Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms

The liver has a central role in metabolism,therefore,it is susceptible to harmful effects of ingested medications(drugs,herbs,and nutritional supplements).Druginduced liver injury(DILI)comprises a range of unexpected reactions that occur after exposure to various classes of medication.Even though most cases consist of mild,temporary elevations in liver enzyme markers,DILI can also manifest as acute liver failure in some patients and can be associated with mortality.Herein,we briefly review available data on DILI induced by targeted anticancer agents in managing classical myeloproliferative neoplasms:Chronic myeloid leukemia,polycythemia vera,essential thrombocythemia,and myelofibrosis.

Neoplastic disease after liver transplantation: focus on de novo neoplasms

De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma(HCC) recurrence have been reported with the use of m TOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs m TOR-inhibitorfree immunosuppression is more efficacious in reducing HCC recurrence.

Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct:A case report

Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor.Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B.This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.

Application of two-phase helical CT in liver neoplasms

Objective: To assess the value of helical CT in the di- agnosis of liver diseases. Methods: 59 patients with different liver diseases were examined by two-phase or multi-phase dynamic helical CT. Results: Small hepatocellular carcinoma showed a higher density in the arterial phase, and a lower den- sity in the portal vein phase. Large hepatic carcino- ma showed a mixed pattern of higher-density in the arterial phase, and a lower density in the portal vein phase. Metastasis carcinoma showed an 'oxeye sign' in the portal vein phase. Hemangioma was not obvi- ously enhanced in the early arterial phase, marginal- ly enhanced in the arterial phase, and equally-densed in the balanced phase. Conclusion: Two-phase helical CT is of value in im- proving the detection rate of or determining the fea- tures of hepatic diseases by two-phase helical dyna- mic scan (2.0-3.0 ml/s speed, and delay time 25- 30 s and 70-85 s).

Liver-directed therapies for liver metastases from neuroendocrine neoplasms:Can laser ablation play any role?

Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases(LM)from neuroendocrine neoplasms(NEN),and minimally invasive,liver-directed therapies are gaining increasing interest.Catheter-based treatments are used in disseminated disease,whereas ablation techniques are usually indicated when the number of LM is limited.Although radiofrequency ablation(RFA)is by far the most used ablative technique,the goal of this opinion review is to explore the potential role of laser ablation(LA)in the treatment of LM from NEN.LA uses thinner needles than RFA,and this is an advantage when the tumors are in at-risk locations.Moreover,the multi-fiber technique enables the use of one to four laser fibers at once,and each fiber provides an almost spherical thermal lesion of 12-15 mm in diameter.Such a characteristic enables to tailor the size of each thermal lesion to the size of each tumor,sparing the liver parenchyma more than any other liver-directed therapy,and allowing for repeated treatments with low risk of liver failure.A recent retrospective study reporting the largest series of LM treated with LA documents both safety and effectiveness of LA,that can play a useful role in the multimodality approach to LM from NEN.

Neuroendocrine neoplasms of liver-A 5-year retrospective clinico-pathological study applying World Health Organization 2010 classification

AIM To study the clinicopathological characteristics of neuroendocrine neoplasms(NEN) on liver samples and apply World Health Organization(WHO) 2010 grading of gastroenteropancreatic(GEP) NEN.METHODS Clinicopathological features of 79 cases of NEN of the liver diagnosed between January 2011 to December 2015 were analyzed. WHO 2010 classification of GEP NEN was applied and the tumors were graded as G1, G2 or G3. Two more categories, D1/2(discordant 1/2) and D2/3(discordant 2/3) were also applied. The D1/2 grade tumors had a mitotic count of G1 and Ki-67 index of G2. The D2/3 tumors had a mitotic count of G2 and Ki-67 index of G3. The follow up details which were available till the end of the study period(December 2015) were collected.RESULTS Of the 79 tumors, 16 each were G1 and G2, and 18 were G3 tumors. Of the remaining 29 tumors, 13 were assigned to D1/2 and 16 were D2/3 grade. Male preponderance was noted in all tumors except for G2 neoplasms, which showed a slight female predilection. The median age at presentation was 47 years(range 10-82 years). The most common presentation was abdominal pain(81%). Pancreas(49%) was the most common site of primary followed by gastrointestinal tract(24.4%) and lungs(18%). Radiologically, 87% of the patients had multiple liver lesions. Histopathologically, necrosis was seen in only D2/3 and G3 tumors. Microvascular invasion was seen in all grades. Metastasis occurred in all grades of primary NEN and the grades of the metastatic tumors and their corresponding primary tumors were similar in 67% of the cases. Of the 79 patients, 36 had at least one follow up visit with a median duration of follow up of 8.5 mo(range: 1-50 mo). This study did not show any impact of the grade of tumor on the short term clinical outcome of these patients.CONCLUSION Liver biopsy is an important tool for clinicopathological characterization and grading of NEN, especially when the primary is not identified. Eighty-seven percent of the patients had multifocal liver lesions irrespective of the WHO grade, indicating a higher stage of disease at presentation. Follow up duration was inadequate to derive any meaningful conclusion on long term outcome in our study patients.

FEASIBILITY STUDY OF AN ULTRASOUND CONTRAST AGENT(LEVOVIST) IN COLOR DOPPLER IMAGING OF LIVER NEOPLASMS

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Prevalence and outcomes of pancreatic cystic neoplasms in liver transplant recipients

AIM To determine the prevalence,characteristics and clinical course of pancreatic cystic neoplasms(PCNs) in liver transplantation(LT) recipients.METHODS We retrospectively studied consecutive patients who underwent LT between January 1998 to April 2016. Clinical and laboratory data were obtained from patient medical records. Imaging findings on computed tomography and magnetic resonance cholangiopancreatography were reviewed by two radiologists.RESULTS During the study period,872 patients underwent cadaveric LT. Pancreatic cysts were identified in 53/872(6.1%) and 31/53(58.5%) were PCNs [28 intraductal papillary mucinous neoplasm(IPMN),2 mucinous cystic neoplasm(MCN),1 serous cystadenoma]. Patients with PCNs exhibited less male predominance(55% vs 73%,P = 0.03) compared to patients without pancreatic cysts. Thirteen patients(42%) were diagnosed with PCN pre-LT while 18 patients(58%) developed PCN post-LT. The median size of PCNs was 13 mm [interquartile range(IQR) 10-20 mm]. All IPMNs were side-branch type. Most PCNs were found in the head and body of pancreas(37% each),followed by the tail(25%). Five patients underwent further evaluation with endoscopic ultrasound. Progress imaging was performed on 81% of patients. PCNs remained stable in size and number in all but 2 patients. During a median follow up of 39 mo(IQR 26-58 mo),the 2(6%) patients with MCN underwent pancreatectomy. No PCN patient developed pancreatic adenocarcinoma,while 5 died from illnesses unrelated to the PCN. Among patients without PCN,1/841(0.1%) developed pancreatic adenocarcinoma.CONCLUSION The prevalence of PCNs in LT recipients was similar to the general population(3.6%,31/872). Side-branch IPMNs do not appear to have accelerated malignant potential in post-LT patients,indicating the current surveillance guidelines are applicable to this group.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.

Transarterial chemoembolization for liver metastases from solid pseudopapillary epithelial neoplasm of pancreas: A case report

Solid pseudo-papillary epithelial neoplasm(SPEN) is a rare epithelial tumor of pancreas with a low malignant potential occurs most commonly in young females. We report a case of 40 years old woman presented withextensive liver metastasis from SPEN of pancreatic body for which she was operated four years ago. Due to the extensive nature of metastatic disease she was offered Transarterial chemoembolisation(TACE) using gemcitabine as chemotherapeutic agent. Short term follow up after a month of TACE with multiphase computed tomography showed > 90% resolution in the viable tumor with significant clinical improvement. TACE ensures targeted delivery of chemotherapeutic drugs in higher doses with least systemic toxicity and is more effective and safe than systemic chemotherapy. TACE with gemcitabine was found to be very effective in our patient with numerous liver metastasis.

Mixed neuroendocrine–nonneuroendocrine neoplasms of the gastrointestinal system:An update

Mixed neuroendocrine-nonneuroendocrine neoplasms(Mi NENs)of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment.Over the years,the diagnostic criteria,classification,and clinical behavior of these tumors have been the subjects of ongoing debate,and the various changes in their nomenclature have strengthened the challenges associated with Mi NENs.This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as Mi NEN,highlight the current diagnostic criteria,summarize the latest data on pathogenesis and provide information on available treatments.Moreover,this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system(GIS).Currently,the Mi NEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma,depending on the organ of origin.Diagnosis is based on the presence of both morphological components in more than 30%of the tumor.However,this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of Mi NEN by biopsy.Furthermore,available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of Mi NEN is not supportive and warrants further investigation.The diagnosis of these tumors is not solely based on immunohistochemical findings.They are not hybrid tumors and both components can act independently;thus,careful grading of each component separately is required.In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection,the aggressive potential of both components has paramount importance in the choice of treatment.Regardless of the organ of origin within the GIS,almost Mi NENs are tumors with poor prognosis and are frequently encountered in the elderly and men.They are most frequently reported in the colorectum,where data from molecular studies indicate a monoclonal origin;however,further studies are required to provide additional support for this origin.

Spontaneous rupture of a mucinous cystic neoplasm of the liver resulting in a huge biloma in a pregnant woman:A case report

BACKGROUND Mucinous cystic neoplasm of the liver(MCN-L)and intraductal papillary neoplasm of the bile duct(IPN-B)are two different types of mucin-producing bile duct tumour that may complicate the course of pregnancy.To the best of our knowledge,we describe herein the first case of MCN-L with spontaneous rupture during pregnancy necessitating complex surgical treatment.CASE SUMMARY A 24-year-old woman was initially admitted to another hospital in October 2018 with signs of jaundice(serum bilirubin level 12 mg/dL)and upper abdominal pain radiating to the left shoulder.Initial magnetic resonance imaging(MRI)of the abdominal cavity revealed a multilocular cystic tumour of the liver hilum(37 mm×40 mm in diameter)located between segments 3 and 4 of the left liver lobe.Six weeks later(December 2018),the patient was found to be 12 wk pregnant and was referred to our institution for further diagnostics and treatment.At admission,a soft,palpable,and tender mass in the left upper abdomen was found.It was determined via MRI(with no intravenous contrast in view of the first-trimester pregnancy)to be a large collection of fluid(19 cm×17 cm×10 cm)located close to the liver hilum and below the left liver lobe.The patient did not undergo any diagnostic or therapeutic procedures nor did they have any abdominal trauma in the preceding weeks.The fluid collection proved to be of biliary origin following percutaneous drainage.Therefore,we concluded this was a spontaneous rupture of an MCN-L with the formation of a biloma.The MRI study also revealed the previously found cystic tumour of the liver hilum communicating with the left hepatic duct,which,together with left hepatic duct dilatation,suggested the diagnosis of IPN-B.The follow-up MRI with intravenous gadolinium contrast performed in the second trimester of pregnancy(week 14)showed,in turn,some features of MCN-L,including enhancement of the internal septations within the cystic liver mass.A precise preoperative differential diagnosis between IPN-B and MCN-L was therefore not possible.The patient was submitted to surgery in the second trimester of pregnancy(week 18).Surgery included a cholecystectomy,left hepatectomy,and concomitant resection of the extrahepatic bile ducts followed by anastomosis of the right hepatic duct with the Roux limb of the jejunum.The post-operative period was uneventful and the patient was discharged 8 days after surgery.The histopathological examination of the resected specimen revealed a final diagnosis of MCN-L with low-grade dysplasia and epithelium surrounded by ovarian-type stromal tissue.The patient delivered a healthy baby girl and both remain well at present,after 2 years of follow-up since surgery.CONCLUSION The differential diagnosis and management of MCN-L and IPN-B may be very challenging,particularly in the setting of pregnancy.When indications for surgery are obvious,the final diagnosis is based on histopathological examination,with ovarian-type stroma being pathognomonic for MCN-L.We believe that the growth of this subepithelial stroma secondary to the high levels of sex hormones produced during pregnancy might have been the main causative factor leading to the tumour rupture with the formation of a biloma in our patient.

Laparoscopic resection of synchronous intraductal papillary mucinous neoplasms:A case report

We describe herein a 68-year-old woman who was diagnosed with a quite rare entity of intraductal papillary mucinous neoplasms(IPMNs) occurring simultaneously in the left lateral lobe of liver and the tail of pancreas.Abdominal computed tomography and magnetic resonance cholangiopancreatography showed a cystic dilatation of the pancreatic duct in the pancreatic tail,which suggested an IPMN,and multiple intrahepatic duct stones in the left lateral lobe.The patient underwent a laparoscopic left lateral hepatolobectomy and spleenpreserving distal pancreatectomy.Intra-operative finding of massive mucin in the dilated bile duct implied an intraductal mucinous tumor in the liver.The diagnosis of synchronous IPMNs in the liver and pancreas was confirmed by pathological examination.The patient was followed up for 6 mo without signs of recurrence.Although several cases of IPMN of liver without any pancreatic association have been reported,the simultaneous occurrence of IPMNs in the liver and pancreas is very rare.To the best of our knowledge,it is the first reported case treated by laparoscopic resection.

Is hepatic neoplasm-related pyogenic liver abscess a distinct clinical entity?

AIM: To compare the clinical characteristics of pyogenic liver abscess (PLA) in patients with and without hepatic neoplasm (HN). METHODS: We performed a retrospective analysis involving patients with PLA. The demographic, clinical features, laboratory and imaging findings, management and outcome of patients with and without HN were studied. RESULTS: From January 2000 to December 2009 inclusive, 318 patients (35 with HN) had PLA, and mean age and comorbidity were comparable between the two groups. More patients with HN experienced right upper quadrant pain (68.6% vs 52.7%, P < 0.04), developed jaundice (14.3% vs 5.7%, P < 0.03) and hepatomegaly (17.1% vs 3.9%, P < 0.01), and had higher serum total bilirubin level (43.3 μmol/L vs 30.0 μmol/L, P = 0.05). Most patients in both groups had PLAs in the right hepatic lobe, and biliary tract disorder was the most common underlying cause (71.4% and 61.8%). However, more PLAs in the HN group were associated with thicker abscess wall (37.1% vs 19.4%, P < 0.01), septal lobulation (77.1% vs 58%, P < 0.02), gaseous cavitation (17% vs 7.8%, P = 0.03), portal thrombophlebitis (11.4% vs 1.8%, P < 0.01) and aerobilia (25.9% vs 5.5%, P < 0.01). Mixed bacterial growth (40% vs 15.2%, P < 0.01) and Gram-negative bacilli (22.8% vs 60.4%, P < 0.01) were dominant isolates in PLAs with and without HN, respectively. Although incidence of the complications was comparable between the two groups, patients with HN had a higher mortality rate than those without (71.4% vs 8.8%, P < 0.01). Multivariate logistic regression analysis revealed underlying active malignancy [odds ratio (OR): 40.45, 95% CI: 14.76-111.65], hypoalbuminemia (OR: 1.22, 95% CI: 1.14-1.38), disseminated intravascular coagulation (OR: 3.32, 95% CI: 1.19-9.69) and acute coronary syndrome (OR: 4.48, 95% CI: 1.08-17.8) were independent risk factors associated with mortality. However, several HN cases, presented concurrently with PLAs, were found to have curative resectable tumors and had good prognosis after surgery. CONCLUSION: PLA associated with HN tends to form a distinct clinical syndrome with a different extent of clinical manifestations, radiological and microbiological features and complications.

Update on surgical treatment of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms(PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential(neurendocrine tumors PNETs) or overt(neuroendocrine carcinomas PNECs) malignant,but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimallyinvasive approaches which should be tailored to the individual patient. Generally,surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs,indications for tumor resection are much wider than for pancreatic adenocarcinoma,in many cases due to the relatively benign tumor biology. Thus,patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands,even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However,poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly singlecenter series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable,ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review,we summarize recent advances in the surgical treatment of PNENs.

Mucinous cystic neoplasm of the liver: A case report

BACKGROUND Mucinous cystic neoplasm of the liver(MCN-L)is a cyst-forming epithelial neoplasm.The most distinguishing feature is the ovarian-type subepithelial stroma on pathological examination.CASE SUMMARY An abdominal ultrasound incidentally revealed a liver tumor in a 32-year-old woman.Physical and laboratory examination results did not reveal any abnormalities.Enhanced abdominal computed tomography(CT)revealed a cystic space measuring 7.2 cm×5.4 cm in the liver.Subsequent CT showed an increase in tumor size.Thus,we performed surgical resection of the tumor and gallbladder.Postoperative histopathological examination confirmed the diagnosis of MCN-L.At the 6-mo of follow-up,no recurrence was observed on ultrasound or CT.CONCLUSION Since preoperative diagnosis of MCN-L is difficult,active surgery is recommended and helpful for the diagnosis and treatment of MCN-L.

Post-hepatectomy liver failure:A timeline centered review

Background: Post-hepatectomy liver failure(PHLF) is a leading cause of postoperative mortality after liver surgery. Due to its significant impact, it is imperative to understand the risk stratification and preventative strategies for PHLF. The main objective of this review is to highlight the role of these strategies in a timeline centered way around curative resection. Data sources: This review includes studies on both humans and animals, where they addressed PHLF. A literature search was conducted across the Cochrane Library, Embase, MEDLINE/Pub Med, and Web of Knowledge electronic databases for English language studies published between July 1997 and June 2020. Studies presented in other languages were equally considered. The quality of included publications was assessed using Downs and Black’s checklist. The results were presented in qualitative summaries owing to the lack of studies qualifying for quantitative analysis. Results: This systematic review with 245 studies, provides insight into the current prediction, prevention, diagnosis, and management options for PHLF. This review highlighted that liver volume manipulation is the most frequently studied preventive measure against PHLF in clinical practice, with modest improvement in the treatment strategies over the past decade. Conclusions: Remnant liver volume manipulation is the most consistent preventive measure against PHLF.

Intraductal papillary neoplasm of the bile duct in liver cirrhosis with hepatocellular carcinoma

A case of intraductal papillary neoplasm of the bile duct (IPNB) arising in a patient with hepatitis B-related liver cirrhosis with hepatocellular carcinoma (HCC) is reported. A 76-year-old man was admitted to our hospital with recurrent HCC. Laboratory data showed that levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were elevated. He died of progressive hepatic failure. At autopsy,in addition to HCCs,an intraductal papillary proliferation of malignant cholangiocytes with fibrovascular cores was found in the dilated large bile ducts in the left lobe,and this papillary carcinoma was associated with an invasive mucinous carcinoma (invasive IPNB). Interestingly,extensive intraductal spread of the cholangiocarcinoma was found from the reactive bile ductular level to the interlobular bile ducts and septal bile ducts and to the large bile ducts in the left lobe. Neural cell adhesion molecule,a hepatic progenitor cell marker,was detected in IPNB cells. It seems possible in this case that hepatic progenitor cells located in reactive bile ductules in liver cirrhosis may have been responsible for the development of the cholangiocarcinoma and HCC,and that the former could have spread in the intrahepatic bile ducts and eventually formed grossly visible IPNB.