Hepatocellular carcinoma presenting as an extrahepatic mass:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is a primary liver tumor generally diagnosed based on radiographic findings.Metastatic disease is typically associated with increased tumor diameter,multifocality,and vascular invasion.We report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography(CT).We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic HCC.CASE SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval,mixed cystic-solid mass.Serial CT evaluations demonstrated steatosis,but no cirrhosis or liver lesions.Endoscopic ultrasound demonstrated a normal-appearing pancreas,biliary tree,and liver.Fine needle aspiration yielded atypical cells.The differential diagnosis included duodenal or pancreatic cyst,lymphoproliferative cyst,stromal or mesenchymal lesions,nodal involvement from gastrointestinal or hematologic malignancy,or duodenal gastrointestinal stromal tumor.After review by a multidisciplinary tumor board,the patient underwent open surgical resection of a 5.2 cm×5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated HCC.Magnetic resonance imaging(MRI)subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement,fatty sparing,and intrinsic T1 hyperintensity.Alpha fetoprotein was 23.3 ng/mL.The patient was diagnosed with HCC with portocaval nodal involvement.Review:We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic HCC.We identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions,and 30 cases of extrahepatic HCC found to be primary,ectopic HCC.CONCLUSION Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of occult primary.In patients with risk factors for HCC and lesions suspicious for metastatic disease,MRI may be integral to identifying small hepatic lesions and differentiating from ectopic HCC.Tumor markers may also have utility in establishing the diagnosis.

Effect of the extrahepatic bile duct anatomy on choledocholithiasis and its clinical significance

BACKGROUND A comprehensive understanding of the extrahepatic bile duct anatomy is vital to guide surgical procedures and perform endoscopic retrograde cholangiography.Anatomical irregularities within the extrahepatic bile duct may increase susceptibility to bile duct stones.AIM To investigate the anatomical risk factors associated with extrahepatic bile ducts in patients diagnosed with choledocholithiasis,with a specific focus on preventing stone recurrence after surgical intervention and endoscopic lithotomy.METHODS We retrospectively analyzed the medical records of 124 patients without choledocholithiasis and 108 with confirmed choledocholithiasis who underwent magnetic resonance cholangiopancreatography examinations at our center between January 2022 and October 2022.Logistic regression analyses were conducted to identify the anatomical risk factors influencing the incidence of common bile duct stones.RESULTS Multivariate logistic regression analysis revealed that several factors independently contributed to choledocholithiasis risk.Significant independent risk factors for choledocholithiasis were diameter of the common hepatic[adjusted odds ratio(aOR)=1.43,95%confidence interval(CI):1.07-1.92,adjusted P value=0.016]and common bile(aOR=1.68,95%CI:1.27-2.23,adjusted P value<0.001)ducts,length of the common hepatic duct(aOR=0.92,95%CI:0.84-0.99,adjusted P value=0.034),and angle of the common bile duct(aOR=0.92,95%CI:0.89–0.95,adjusted P value<0.001).The anatomical features of the extrahepatic bile duct were directly associated with choledocholithiasis risk.Key risk factors include an enlarged diameter of the common hepatic and bile ducts,a shorter length of the common hepatic duct,and a reduced angle of the common bile duct.

Comparison of the clinical effects of dual-modality endoscopy and traditional laparotomy for the treatment of intra-and extrahepatic bile duct stones

BACKGROUND Bile duct stones(BDSs)may cause patients to develop liver cirrhosis or even liver cancer.Currently,the success rate of surgical treatment for intrahepatic and extrahepatic BDSs is not satisfactory,and there is a risk of postoperative complic-ations.AIM To compare the clinical effects of dual-modality endoscopy(duodenoscopy and laparoscopy)with those of traditional laparotomy in the treatment of intra-and extrahepatic BDSs.METHODS Ninety-five patients with intra-and extrahepatic BDSs who sought medical services at Wuhan No.1 Hospital between August 2019 and May 2023 were selected;45 patients in the control group were treated by traditional laparotomy,and 50 patients in the research group were treated by dual-modality endoscopy.The following factors were collected for analysis:curative effects,safety(incision infection,biliary fistula,lung infection,hemobilia),surgical factors[surgery time,intraoperative blood loss(IBL)volume,gastrointestinal function recovery time,and length of hospital stay],serum inflammatory markers[tumor necrosis factor(TNF)-α,interleukin(IL)-6,and IL-8],and oxidative stress[glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),malondialdehyde(MDA),and advanced protein oxidation products(AOPPs)].RESULTS The analysis revealed markedly better efficacy(an obviously higher total effective rate)in the research group than in the control group.In addition,an evidently lower postoperative complication rate,shorter surgical duration,gastrointestinal function recovery time and hospital stay,and lower IBL volume were observed in the research group.Furthermore,the posttreatment serum inflammatory marker(TNF-α,IL-6,and IL-8)levels were significantly lower in the research group than in the control group.Compared with those in the control group,the posttreatment GSH-Px,SOD,MDA and AOPPs in the research group were equivalent to the pretreatment levels;for example,the GSH-Px and SOD levels were significantly higher,while the MDA and AOPP levels were lower.CONCLUSION Dual-modality endoscopy therapy(duodenoscopy and laparoscopy)is more effective than traditional laparotomy in the treatment of intra-and extrahepatic BDSs and has a lower risk of postoperative complications;significantly shortened surgical time;shorter gastrointestinal function recovery time;shorter hospital stay;and lower intraop-erative bleeding volume,while having a significant inhibitory effect on excessive serum inflammation and causing little postoperative oxidative stress.

Nursing Effect of Rapid Rehabilitation Surgery Concept in Laparoscopic Surgery for Extrahepatic Bile Duct Stones

Objective: To explore the application value of rapid rehabilitation concept in patients with extrahepatic bile duct stones under laparoscopy during perioperative period. Methods: 90 patients with extrahepatic bile duct stones treated in our hospital from January 2022 to February 2023 were selected as the research object and randomly divided into the study group and the control group. The control group was given routine care, and the observation group was given rapid surgical rehabilitation care. The postoperative anal exhaust time, first meal time, early activity time, pain time, abdominal drainage tube removal time, hospitalization time and complication rate were compared between the two groups. The independent sample T test was used for the measurement data, and the x2 test was used for the counting data, and the difference was statistically significant (P Results: The postoperative anal exhaust time, first meal time, early activity time, pain time, abdominal drainage tube removal time and hospitalization time in the study group were shorter than those in the control group (all P Conclusion: The concept of rapid rehabilitation can significantly improve the perioperative nursing effect of patients with extrahepatic bile duct stones and accelerate their rehabilitation, which is worth improving and popularizing.

Application of transmesenteric vein extrahepatic portosystemic shunt in treatment of symptomatic portal hypertension with cavernous transformation of portal vein

Purpose:To evaluate the feasibility and efficacy of a transmesenteric vein extrahepatic portosystemic shunt(TmEPS)for the treatment of cavernous transformation of the portal vein(CTPV).Materials and methods:The clinical data of 20 patients with CTPV who underwent TmEPS between December 2020and January 2022 at Henan Provincial People’s Hospital were retrospectively collected.The superior mesenteric vein(SMV)trunk was patent or partially occluded in these patients.An extrahepatic portosystemic shunt between the inferior vena cava and the SMV was established using a stent graft through an infraumbilical median longitudinal mini-laparotomy.The technical success,efficacy,and complication rates were evaluated,and the preand postoperative SMV pressures were compared.Patients’clinical outcomes and shunt patency were assessed.Results:TmEPS was successfully performed in 20 patients.The initial puncture success rate of the balloon-assisted puncture technique is 95%.The mean SMV pressure decreased from 29.1±2.9 mmHg to 15.6±3.3 mmHg(p<0.001).All symptoms of portal hypertension resolved.No fatal procedural complications occurred.During the follow-up period,hepatic encephalopathy occurred in two patients.The remaining patients remained asymptomatic.All shunts were patent.Conclusions:TmEPS is a feasible,safe,and effective treatment option for patients with CTPV.

Hepatopancreatoduodenectomy for the treatment of extrahepatic cholangiocarcinoma

To the Editor:Extrahepatic cholangiocarcinoma(ECC)is an uncommon neoplasm associated with a poor prognosis[1-3].Surgical resection represents the only curative approach,since systemic treatments have scarce efficacy in achieving disease control.However,only 10%-40%of patients with ECC are resectable at diagnosis[1].Ma-jor hepatectomy and portal lymphadenectomy are usually required for hilar ECC,while pancreatoduodenectomy is the standard operation for distal ECC[3-5].However,ECC may spread horizon-tally along the biliary tree,causing tumor involvement of the entire extrahepatic biliary system.In these circumstances,hep-atopancreatoduodenectomy(HPD)has been proposed as a pro-cedure with curative intent[2,6,7].

Clinical study of extrahepatic biliary adenoma

BACKGROUND Biliary adenomas that occur in the extrahepatic biliary tree are rare.It is difficult to distinguish it from cholangiocarcinoma or cholangiolithiasis by various imaging examinations,and it is very easy to be misdiagnosed.AIM To evaluate the cumulative experiences including clinical characteristics and treatments of nine patients diagnosed with extrahepatic biliary adenoma admitted to the First Affiliated Hospital of Xi’an Jiaotong University from 2016 to 2022.METHODS A total of nine patients were included in our study.The laboratory examinations,disease diagnosis,therapy and pathological characteristics,and follow-up of every patient were evaluated.RESULTS Our cohort consisted of six females and three males with an average diagnosis age of 65.1 years(range 46-87).Six extrahepatic biliary adenomas were located in the common bile ducts and three in the hepatic duct.On initial presentation,all of the patients have symptom of biliary origin,including obstructive jaundice(4/9,44.4%),abdominal pain(6/9,66.7%),and fever(3/9,33.3%).Preoperative imaging examination considered bile duct carcinoma in 6 cases and bile duct calculi in 3 cases.All the patients received surgical treatment and were confirmed by pathology as biliary adenoma.The symptoms improved significantly in all 9 patients after surgery.Seven of nine patients recovered well at follow-up without tumor recurrence.One patient died 2 mo after the surgery due to heart failure.One patient developed jaundice again 8 mo after surgery,underwent endoscopic retrograde cholangiopancreatography and biliary stent placement.CONCLUSION Benign extrahepatic biliary tumors are rare and difficult to diagnosis preoperatively.Intraoperative choledochoscopy and timely biopsy may offer great advantages.

An Analysis of Prospective Outcome of Re-resection for Recurrent Live Cancer and Extrahepatic Metastases,a Follow-up of 267\Cass

Objective To evaluate the prospective outcome and summarize experience in re-resection for recurrent liver cancer and extrahepatic metastases. Methods The clinical data of 267 patients with recurrent primary liver cancer (PLC) after re-resection from January 1960 to July 2000 were retrospectively analyzed. Re-hepatectomy was performed on 205 cases, resection of extrahepatic metastases on 51 cases and combined resection of recurrent liver cancer and extrahepatic metastases on 11 cases. The clinico-pathologic features, operation type and survival were compared. Results The types of liver re-resection included left lateral lobectomy in 11.2% of patients, hemihepatetomy and extended hemi-hepatectomy in 4.4%, local radical resection in 68.3%, other subsegmentectomy in 17.1%. The peak recurrence rate (64.4%) occurred at 1–2 years. The overall 1-, 3, 5- and 10-year survival rates after second resection were 81.0%, 40.3%, 19.4% and 9.0% respectively, while they were 77.5%, 29.8%, 13.2% and 6.61% respectively after the third resection. The median survival time was 44 months. The re-resection with extrahepatic metastases also provided the possibility of longer survival. Conclusion The results suggest that subsegmentectomy and local excision is appropriate for the hepatic repeat resection. The peak recurrence may be correlated with portal thrombus and operative factor. The re-resection can be indicated not only in intrahepatic recurrent metastases but also in extrahepatic metastases in selected patients. Re-resection has become the treatment of choice for recurrence of PLC, as neither chemotherapy nor other nonsurgical therapies can achieve such favorable results. Key words prospective outcome - re-resection - primary liver cancer - recurrence - extrahepatic metastases

Meso-Rex bypass for the management of extrahepatic portal vein obstruction in adults(with video)

Background:Extrahepatic portal vein obstruction(EHPVO)results in severe portal hypertension(PHT)leading to severely compromised quality of life.Often,pharmacological and endoscopic management is unable to solve this problem.Restoring hepatic portal flow using meso-Rex bypass(MRB)may solve it.This procedure,uncommon in adult patients,is considered the treatment of choice for EHPVO in children.Methods:From 1997 to 2018,8 male and 6 female adults,with a median age of 51 years(range 22-66)underwent MRB procedure for EHPVO at the University Hospitals Saint-Luc in Brussels,Belgium.Symp-toms of PHT were life altering in all but one patient and consisted of repetitive gastro-intestinal bleedings,sepsis due to portal biliopathy,and/or severe abdominal discomfort.The surgical technique consisted in interposition of a free venous graft or of a prosthetic graft between the superior mesenteric vein and the Rex recess of the left portal vein.Results:Median operative time was 500 min(range 300-730).Median follow-up duration was 22 months(range 2-169).One patient died due to hemorrhagic shock following percutaneous transluminal interven-tion for early graft thrombosis.Major morbidity,defined as Clavien-Dindo score≥III,was 35.7%(5/14).Shunt patency at last follow-up was 64.3%(9/14):85.7%(6/7)of pure venous grafts and only 42.9%(3/7)of prosthetic graft.Symptom relief was achieved in 85.7%(12/14)who became asymptomatic after MRB.Conclusions:Adult EHPVO represents a difficult clinical condition that leads to severely compromised quality of life and possible life-threatening complications.In such patients,MRB represents the only and last resort to restore physiological portal vein flow.Although successful in a majority of patients,this procedure is associated with major morbidity and mortality and should be done in tertiary centers expe-rienced with vascular liver surgery to get the best results.

Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma

AIM: To assess the clinical features and prognosis of 151 patients with extrahepatic metastases from primary hepatocellular carcinoma (HCC), and describe the treatment strategy for such patients. METHODS: After the diagnosis of HCC, all 995 consecutive HCC patients were followed up at regular intervals and 151 (15.2%) patients were found to have extrahepatic metastases at the initial diagnosis of primary HCC or developed such tumors during the follow-up period. We assessed their clinical features, prognosis, and treatment strategies. RESULTS: The most frequent site of extrahepatic metastases was the lungs (47%), followed by lymph nodes (45%), bones (37%), and adrenal glands (12%). The cumulative survival rates after the initial diagnosis of extrahepatic metastases at 6, 12, 24, and 36 mo were 44.1%, 21.7%, 14.2%, 7.1%, respectively. The median survival time was 4.9 mo (range, 0-37 mo). Fourteen patients (11%) died of extrahepatic HCC, others died of primary HCC or liver failure. CONCLUSION: The prognosis of HCC patients with extrahepatic metastases is poor. With regard to the cause of death, many patients would die of intrahepatic HCC and few of extrahepatic metastases. Although most of HCC patients with extrahepatic metastases should undergo treatment for the primary HCC mainly, treatment of extrahepatic metastases in selected HCC patients who have good hepatic reserve, intrahepatictumor stage (T0-T2), and are free of portal venous invasion may improve survival.

Catheter tract implantation metastases associated with percutaneous biliary drainage for extrahepatic cholangiocarcinoma

AIM： To estimate the incidence of catheter tract implantation metastasis among patients undergoing percutaneous transhepatic biliary drainage （PTBD） for extrahepatic cholangiocarcinoma, and to provide data regarding the management of this unusual complication of PTBD by reviewing cases reported in the literature. METHODS： A retrospective analysis of 67 consecutive patients who underwent PTBD before the resection of extrahepatic cholangiocarcinoma was conducted. The median follow-up period after PTBD was 106 too. The English language literature （PubMed, National Library of Medicine, Bethesda, MD, USA）, from .lanuary 1966 through December 2004, was reviewed. RESULTS： Catheter tract implantation metastasis developed in three patients. The cumulative incidence of implantation metastasis reached a plateau （6%） at 20 mo after PTBD. All of the three patients with implantation metastasis died of tumor progression at 3, 9, and 20 mo after the detection of this complication. Among the 10 reported patients with catheter tract implantation metastasis from extrahepatic cholangiocarcinoma （including our three patients）, two survived for more than 5 years after the excision of isolated catheter tract metastases. CONCLUSION： Catheter tract implantation metastasis is not a rare complication following PTBD for extrahepatic cholangiocarcinoma. Although the prognosis for patients with this complication is generally poor, the excision of the catheter tract may enable survival in selected patients with isolated metastases along the catheter tract.

Portal vein thrombosis: Etiology and clinical outcome of cirrhosis and malignancy-related non-cirrhotic, non-tumoral extrahepatic portal venous obstruction

The etiology and pathogenesis of portal vein thrombosis are unclear. Portal venous thrombosis presentation differs in cirrhotic and tumor-related versus non-cirrhotic and non-tumoral extrahepatic portal venous obstruction (EHPVO). Non-cirrhotic and non-tumoral EHPVO patients are young and present with well tolerated bleeding. Cirrhosis and tumor-related portal vein thrombosis patients are older and have a grim prognosis. Among the 118 patients with portal vein thrombosis, 15.3% had cirrhosis, 42.4% had liver malignancy (primary or metastatic), 6% had pancreatitis (acute or chronic), 5% had hypercoagulable state and 31.3% had idiopathy, 12% had hypercoagulable state in the EHPVO group.

Treatment of a patient with obstructive jaundice and extrahepatic portal hypertension

BACKGROUND: Recurrence of inflammation in the extrahepatic bile duct can lead to bile duct stenosis' obstructive jaundice and cavernous transformation of the portal vein. The latter can develop into extrahepatic portal hypertension (PHT). It is difficult to establish the correct method for treating these conditions. METHODS: At another hospital, a 51-year-old man developed PHT as a result of endoscopic retrograde cholangiopancreatography and endoscopic nasobiliary drainage to relieve cholelithiasis and obstructive jaundice. We dealt with the biliary tract obstruction through percutaneous transhepatic cholangial drainage (PTCD), followed by selective devascularization and a shunt operation 2 weeks after the disappearance of jaundice. Three months after cholecystojejunostomy, there were no obvious changes around the bile duct. RESULT: The patient recovered uneventfully and was discharged 14 days after operation. CONCLUSION: For this patient, surgery in stages was the best choice. The most suitable method to decrease jaundice is PTCD.

Etiology and long-term outcome of extrahepatic portal vein obstruction in children

AIM:To study the management and outcome of children with extrahepatic portal vein obstruction(EHPVO) in a whole country population.METHODS:A nationwide multicenter retrospective case series of children with EHPVO was conducted.Data on demographics,radiographic studies,laboratory workup,endoscopic and surgical procedures,growth and development,were extracted from the patients' charts.Characteristics of clinical presentation,etiology of EHPVO,management and outcome were analyzed.RESULTS:Thirty patients,13 males and 17 females,19(63.3%) Israeli and 11(36.7%) Palestinians,were included in the analysis.Age at presentation was 4.8± 4.6 years,and mean follow-up was 4.9±4.3 years.Associated anomalies were found in 4 patients.The incidence of EHPVO in Israeli children aged 0-14 years was 0.72/million.Risk factors for EHPVO were detected in 13(43.3%)patients,including 9 patients(30%) with perinatal risk factors,and 4 patients(13.3%) with prothrombotic states:two had low levels of protein S and C,one had lupus anticoagulant,and one was homozygous for methyltetrahydrofolate reductase mutations.In 56.6% of patients,no predisposing factors were found.The most common presenting symptoms were an incidental finding of splenomegaly(43.3%),and upper gastrointestinal bleeding(40%).No differences were found between Israeli and Palestinian children with regard to age at presentation,etiology and clinical symptoms.Bleeding occurred in 18 patients(60%),at a median age of 3 years.Sclerotherapy or esophageal banding was performed in 20 patients.No sclerotherapy complications were reported.Portosystemic shunts were performed in 11 patients(36.6%),at a median age of 11(range 3-17)years:splenorenal in 9,mesocaval in 1,and a meso-Rex shunt in 1 patient.One patient underwent splenectomy due to severe pancytopenia.Patients were followed up for a median of 3(range 0.5-15)years.One patient died aged 3 years due to mucopolysaccharidase deficiency type Ⅲ.None of the patients died due to gastrointestinal bleeding.CONCLUSION:EHPVO is a rare disorder.The etiological factors are still mostly unknown,and the endoscopic and surgical treatment options ensure a good long-term prognosis.

Alterations of seminal and hormonal parameters:An extrahepatic manifestation of HCV infection?

AIM： To evaluate the possible influences of HCV infection and relative antiviral treatment on seminal parameters and reproductive hormonal serum levels. METHODS： Ten male patients with HCV-related chronic hepatitis and 16 healthy male volunteers were studied. In all subjects seminal parameters （nemaspermic concentration, progressive motility, morphology） and hormonal levels were determined. Seminal parameters and inhibin B, follicle-stimulating hormone, luteinizing hormone, total and free testosterone, estradiol, prolactine in patients were measured after six and twelve months of antiviral combined （interferon ± ribavirin） treatment. RESULTS： Patients before treatment showed a significantly lower nemaspermic motility and morphology as well as lower inhibin B and free testosterone levels than controls. Inhibin B levels in cases were improved six and 12 mo after treatment in five responders （161.9 ± 52.8 pg/mL versus 101.7 ± 47.0 pg/mL and 143.4 ± 46.1 pg/ mL versus 95.4 ± 55.6 pg/mL, respectively）. Hormonal pattern of patients did not significantly change after treatment, with the exception of estradiol levels with an initial reduction and an overall subsequent increment （19.7 ± 6.4 pg/mL versus 13.6 ± 5.0 pg/mL versus 17.3 ± 5.7 pg/mL）. However in 1-year responders a significant increment of free testosterone （14.2 ± 2.54 pg/mL versus 17.1 ± 2.58 pg/mL） occurred. An impairment of nemaspermic morphology occurred, while other seminal parameters did not change significantly during antiviral treatment. CONCLUSION： Patients with HCV infection show worse spermatic parameters than controls, suggesting a possible negative influence of virus on spermatogenesis, with further mild impairment during antiviral treatment. However therapy could improve the spermatic function, as suggested by the increased inhibin B levels and improved hormonal pattern in responders. Further studies are needed to confirm these preliminary intriguing results.

Positron emission tomography/computer tomography in guidance of extrahepatic hepatocellular carcinoma metastasis management

Hepatocellular carcinoma （HCC） is one of the most common primary cancers in the world. Surgery is the gold standard for treatment of patients with HCC. Recurrence and metastasis are the major obstacles to further improve the prognosis of HCC. Most recurrences are intrahepatic. However, 30% of the recurrences are extrahepatic. The role of resection in intrahepatic recurrences is widely accepted. The role of resection in extrahepatic HCC recurrence and metastasis is not well established. 18F fluorodeoxyglucose （18F-FDG） positron emission tomography/computer tomography （PET/CT） is useful in detecting distant metastasis from a variety of malignancies and shows superior accuracy to conventional imaging modalities in identification of intrahepatic and extrahepatic metastasis. We present one patient with one new isolated omental lymph node metastasis, who had a history of huge HCC resected six years ago. The metastatic focus was identified with 18 F-FDG PET/CT and resected. The follow-up revealed good prognosis with a long-term survival potential after resection of the omental lymphatic metastasis.

Extrahepatic collaterals and liver damage in embolotherapy for ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery

AIM: To evaluate the effects of extrahepatic collaterals to the liver on liver damage and patient outcome after embolotherapy for the ruptured hepatic artery pseudoa- neurysm following hepatobiliary pancreatic surgery. METHODS: We reviewed 9 patients who underwent transcatheter arterial embolization (TAE) for the ruptured hepatic artery pseudoaneurysm following major hepato- biliary pancreatic surgery between June 1992 and April 2006. We paid special attention to the extrahepatic arte- rial collaterals to the liver which may affect post-TAE liver damage and patient outcome. RESULTS: The underlying diseases were all malignan- cies, and the surgical procedures included hepatopancre- atoduodenectomy in 2 patients, hepatic resection with removal of the bile duct in 5, and pancreaticoduodenec- tomy in 2. A total of 11 pseudoaneurysm developed: 4 in the common hepatic artery, 4 in the proper hepatic artery, and 3 in the right hepatic artery. Successful he- mostasis was accomplished with the initial TAE in all patients, except for 1. Extrahepatic arterial pathways to the liver, including the right inferior phrenic artery, the jejunal branches, and the aberrant left hepatic artery, were identified in 8 of the 9 patients after the completion of TAE. The development of collaterals depended on the extent of liver mobilization during the hepatic resection, the postoperative period, the presence or absence of an aberrant left hepatic artery, and the concomitant arte- rial stenosis adjacent to the pseudoaneurysm. The liver tolerated TAE without significant consequences when at least one of the collaterals from the inferior phrenic ar-tery or the aberrant left hepatic artery was present. One patient, however, with no extrahepatic collaterals died of liver failure due to total liver necrosis 9 d after TAE. CONCLUSION: When TAE is performed on ruptured hepatic artery pseudoaneurysm, reduced collateral path- ways to the liver created by the primary surgical proce- dure and a short postoperative interval may lead to an unfavorable outcome.

Feasibility and efficacy evaluation of metallic biliary stents eluting gemcitabine and cisplatin for extrahepatic cholangiocarcinoma

BACKGROUND Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma(ECC).However,current biliary stents that are widely used in clinical practice showed no antitumor effect.Drug-eluting stents(DESs)may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis.AIM To develop novel DESs coated with gemcitabine(GEM)and cisplatin(CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity.METHODS Stents coated with different drug-eluting components were prepared by the mixed electrospinning method,with poly-L-lactide-caprolactone(PLCL)as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents.Four different DESs were manufactured with four drug-loading ratios(5%,10%,15%,and 20%),including bare-loaded(PLCL-0),single-drug-loaded(PLCL-GEM and PLCL-CIS),and dual-drug-loaded(PLCL-GC)stents.The drug release property,antitumor activity,and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC.RESULTS The in vitro drug release study showed the stable,continuous release of both GEM and CIS,which was sustained for over 30 d without an obvious initial burst,and a higher drug-loaded content induced a lower release rate.The drug-loading ratio of 10%was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity.All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo;in addition,the dual-loaded nanofilm(PLCL-GC)had a significantly better effect than the single-drug-loaded nanofilms(P<0.05).No significant differences in the serological analysis(P>0.05)or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract.CONCLUSION This novel PLCL-GEM and CIS-eluting stent maintains continuous,stable drug release locally and inhibits tumor growth effectively in vitro and in vivo.It can also be used safely in normal porcine bile ducts.We anticipate that it might be considered an alternative strategy for the palliative therapy of ECC patients.

Neuroendocrine carcinoma of the extrahepatic bile duct: Case report and literature review

Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is rare, and only 22 cases have been reported. Only two of these were large-cell NEC (LCNEC); the vast majority were small-cell NEC. Here, we report a third case of LCNEC of the extrahepatic bile duct. A 76-year-old male presented to a local hospital with painless jaundice. Imaging studies revealed a tumor at the hepatic hilum. The patient underwent right hepatic lobectomy, bile duct resection, and cholecystectomy. The resection specimen showed a 5.0-cm invasive neoplasm involving the hilar bile ducts and surrounding soft tissue. Histologically, the tumor consisted of nests of medium to large cells with little intervening stroma. The tumor invaded a large portal vein branch. All four excised lymph nodes were positive for metastasis, and metastatic deposits were also present in the gallbladder wall. The tumor was diffusely positive for synaptophysin and focally positive for chromogranin A. Approximately 70%-80% of the tumor cells were positive for Ki-67, indicating strong proliferative activity. A diagnosis of LCNEC was made. A few bile ducts within and adjacent to the invasive tumor showed dysplasia of the intestinal phenotype and were focally positive for synaptophysin and chromogranin A, suggesting that the dysplastic intestinal-type epithelium played a precursor role in this case. A postoperative computer tomography scan revealed rapid enlargement of the abdominal and retroperitoneal lymph nodes. The patient died 21 d after the operation. NEC of the bile duct is an aggressive neoplasm, and its biological characteristics remain to be better defined.

Efficacy of capecitabine and oxaliplatin regimen for extrahepatic metastasis of hepatocellular carcinoma following local treatments

AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic metastasis of HCC after local treatment were prospectively enrolled. The CapeOx regimen consisted of capecitabine 1000 mg/m 2 taken orally twice daily on days 1-14, and oxaliplatin was administered at a total dose of 100 mg/m 2 on day 1. The treatment was repeated every 3 wk until disease progression or unaccetablle toxicity. Efficacy and safety were assessable for all enrolled patients. The primary objective of this study was to assess the overall response rate. The secondary objectives were to evaluate the overall survival (OS), the time to tumor progression (TTP) and the toxicity profile of the combined strategy. TTP and OS were assessed by the Kaplan-Meier method and differences between the curves were analyzed using the log-rank test. The statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, United States) was used for statistical analysis. All P values were 2-tailed, with statistical significance defined byP ≤ 0.05. RESULTS: Thirty-two patients were assessable for efficacy and toxicity. The median follow-up duration was 15 mo (range, 12-20 mo). At the cut-off date of March 31, 2012, 27 patients died due to tumor progression and one patient died of myocardial infarction. Four patients were still alive (three patients with disease progression). OR was 21.9% (n = 7), the stabilization rate was 40.6% (n = 13), and the disease control rate was 62.5%. The responses lasted from 4 to 19 mo (median, 6 mo). Median TTP was 4.2 mo (95%CI: 2.5-7.4), and the median OS time was 9.2 mo (95%CI: 6.5-17.8). The 1-year survival rate was 43.6% (95%CI: 29.0-66.0). In a multivariate analysis, OS was significantly longer in patients with a Child-Pugh class A compared with class B patients (P = 0.014), with a median OS of 10.1 mo vs 5.4 mo, and there were trends towards longer OS (P = 0.065) in patients without portal vein tumor thrombosis. There were no significant effects of age, gender, performance status, cirrhosis, metastatic sites, and level of alpha fetoprotein (AFP) or hepatitis B virus-DNA on OS. Among the 22 patients with elevated AFP levels at baseline (≥ 400 ng/mL), the level fell by more than 50% during treatment in 6 patients (27.3%). The most frequent treatment-related grade 3 to 4 toxicities included leucopenia/neutropenia, transient elevation of aminotransferases, handfoot syndrome and fatigue. CONCLUSION: CapeOx showed modest anti-tumor activity in metastatic HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further study for these patients.