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.

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.

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

The purpose of this study was to determine the efficacy of using an ultrasound contrast agent(levovist)to enhance the color Doppler imaging of liver neoplasms.Thirty patients with hepatic tumors were enrolled in this study.After intravenous administration of levovist,the color Doppler signals of normal hepatic vessels were enhanced.In various hepatic tumors,the different patterns of tumor vascularity were observed,which had not been demonstrated in conventional non contrast color Doppler imaging.In 11 of 16 patients with hepatocarcinoma,additional color Doppler signals were observed in the central part of the tumors.On the contrary,3 patients with metastatic liver lesions the enhanced color Doppler signals appear only at the peripheral of tumors.A typical rim like color enhancement was seen in 2 of the 3 cases.In six patients with hepatic hemangiomas contrast enhanced color Doppler imaging demonstrated the blood vessels at the margin of the neoplasms.Contrast enhanced color Doppler imaging improves the visualization of the hepatic neoplasm vascularity.This technique holds great promise for detecting small liver tumors and differentiating hepatic neoplasms.

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).

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.

Laparoscopic hepatectomy for liver neoplasms in 15 cases

Objective： The aim of our study was to retrospectively analyze 15 patients＇ clinical materials with laparoscopic resection of liver neoplasms. Methods： From December 2007, a total of 15 patients with liver neoplasms were performed with laparoscopic hepatectomy, and their clinical materials, perioperative dates, postoperative complications, postoperative recovery and short-term curative effects were analyzed and summarized respectively. Results： Laparoscopic hepatectomy （LH） were performed in 15 patients, including 1 case underwent laparoscopic hepatic left Iobectomy, 1 case of left lateral hepatectomy, 13 cases of partial liver resection. Fourteen cases of total laparoscopic liver resections for liver neoplasms, 1 case of hand-assisted laparoscopic liver resection of the tumor, there was no conversion to open approach. Of the 15 patients with liver neoplasms, 13 cases of hepatic neoplasms with the maximum diameter was 8 cm× 8 cm × 9 cm, 9 cases of the borderline micro hepatocellular carcinoma （MHCC） with the diameter not more than 2 cm, 3 cases of hepatic benign tumor. The mean operation time was （120 ± 30） min, and the intraoperative average hemorrhage was 100 mL, beginning to eat and get out of bed following 1-2 days of operation. The average postoperative hospitalization was 8 days, WBC, ALl＇, AST, albumin, bilirubin returned to normal after one week of operation. There were no postoperative complications such as hemorrhage, bile leakage or air embolism etc. Twelve patients with HCC were confirmed by postoperative pathology, 1 case of liver smooth muscle lipoma, 2 case of hepatic hemangioma. By one year of followed-up in 12 cases of HCC, the longest survival was 38 months, and no recurrence or death, 1 year survival rate was 100%. Conclusion： Among the choice of cases, the advantages of LH for liver neoplasms compared with open surgery were less trauma, faster recovery and less blood loss. it is safe and effective for choosing a reasonable surgical indication, especially for peripheral micro hepatocellular carcinoma.

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.

Establishment of a mdr1 Multidrug Resistant Model of Orthotopic Transplantation of Liver Carcinoma on Nude Mice

To develop a new method of inducing mdrl multidrug resistance by establishinga nude mice model of orthotopic transplantation of liver carcinoma by sporadic abdominalchemotherapy at intervals. Methods: Hepatocellular carcinoma HepG2 cell was cultured and injectedsubcutaneously to form the tumor-supplying mice. The tumor bits from the tumor-supplying mice wereimplanted under the envelope of the mice liver and induced by abdominal chemotherapy withPharmorubicin. Physical examination, ultrasonography, spiral CT and operative inspection were usedto examine tumor progression. RT-PCR and immunohistochemistry were adopted to detect the expressionof mdr1-mRNA and its encoded protein P-gp protein (P-gp). Results: There was no operative dead, therate of implanting tumor successfully was 88% (22/25), the rate of implanting secondly successfullywas 100% (3/3), and the rate of inducing successfully was 80% (16/20). The expression of mdrl-mRNAand the P-gp in the inducing group was 23 folds and 13 folds in the control group respectively.Conclusion: We have established an in vivo model of mdr using nude mice transplanted with orthotopicliver neoplasm coupled to chemotherapy.

Liver metastasis models of human colorectal carcinoma established in nude mice by orthotopic transplantation and their biologic characteristics

AIM To establish a liver metastasis model of human colorectal carcinoma in nude mice.METHODS Orthotopic transplantation of histologically intact colorectal tissues from patients into colorectal mucosa of nude mice. Tumorgenicity, invasion, metastasis and morphological characteristics of the transplanted tumors were studied by light microscopy, electron microscopy and immunohistochemistry.RESULTS Liver metastasis models of human colon carcinoma (HCA-HMN-1) and human rectal carcinoma (HRA-HMN-2) were established after screening from 34 colorectal carcinomas. They had been passaged in vivo for 18 and 21 generations respectively. There were lymphatic, hemotogenous and implanting metastasesis. CEA secretion was maintained after transplantation. The primary and liver metastatic tumors were similar to the original human carcinoma in histopathological and ultrastructural features, DNA content and chromosomal karyotype.CONCLUSION The liver metastasis models provide useful tools for the study of mechanism of metastasis and its treatment of human colorectal cancer.INTRUDUCTIONSome models of nude mice that fresh human colorectal carcinoma tissue or cells were successfully transplanted subcuteneously have been reported at home and abroad[1,2]. But until now there has been no report on a liver metastasis model of human colorectal carcinoma established by orthotopic transplantation in nude mice in China. Based on our previous models of human liver and pancreas carcinoma by orthotopic transplantation[3,4], we established liver metastasis models of colon and rectum carcinoma with a spontaneous metastasis rate of 100%.

Percutaneous cryoablation after chemoembolization of liver carcinoma: report of 34 cases

OBJECTIVE: To assess the indications, efficacy and clinical significance of percutaneous cryoablation for liver carcinoma after transcatheter liver artery chemoembolization (TACE). METHODS: Thirty-four patients with histologically or clinically confirmed primary or metastatic carcinomas were treated with TACE. One week to 1 month later, they were treated percutaneously under ultrasound guidance using cryosurgical system in the period of July 2001 -June 2002. All patients were followed up to determine serum tumor marker, CT scans, MRI images or ultrasound images. RESULTS: This therapy was performed in 34 patients including 32 patients with Child A liver reserve, 2 patients with Child B and no patient with Child C. There were 28 patients with primary liver cancer and 6 patients with metastatic liver cancer. During the follow-up period (3 to 15 months), 41.1% patients were recognized clinically cured because the serum tumor markers became normal, or CT scans and MRI images revealed that the lesion became completely necrotic. 44.1% patients were recognized effectively treated. CONCLUSIONS: Percutaneous cryoablation combined with TACE is a choice of treatment for liver carcinoma. It is minimally invasive, safe and effective for those patients with liver cancer unsuitable for surgery.

Source of blood supply of liver cavernous hemangioma and sclerosis and embolization treatment

AIM To investigate the source of blood supply of carvenous hemangioma of liver (CHL) and provide a feasibile treatment for CHL via hepatic artery. METHODS Ⅰ. Origin of blood supply of CHL: portovenography, hepatic arteriography and portal vein staining were performed in 5 patients. Two casts of hepatic blood vessels from resected specimen were observed. Ⅱ. Clinical data: Among 75 patients (30 males, 45 females, aged 25～57 years with a mean of 37 4). 56 were of solitary type (44 on the right lobe, 12 on the left with 4 having intraparenchymatoma) and 19 were of multiple type (9 on the right, 2 the left, 8 whole liver). Twenty two patients were treated by sclerosis, 50 by embolization via hepatic artery and 3 were excised. RESULTS In 5 cases with portography, the contrast medium did not enter the tumor, the tumor appeared as low denty area and the intrahepatic branches of portal vein were pushed aside. In 5 cases with portal vein staining, the normal liver parenchyma was stained deep blue, and the tumor was not stained. The tumor area appeared as a round vacant cavity in 2 specimen casts. In 72 patients treated with sclerosis a or embolization via hepatic artery or through interventional method, the tumors diminished by 10%～30% in diameter and no tumors grew larger. CONCLUSION The blood supply of CHL originates from the hepatic artery. Tumors treated with sclerosis and emblization decreased in size or got fiberized.

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.

CT assessment of liver hemodynamics in patients with hepatocellular carcinoma after argon-helium cryoablation

BACKGROUND:Assessment of tumor response after argonhelium cryoablation is critical in guiding future therapy for unresectable hepatocellular carcinoma.This study aimed to evaluate liver hemodynamics in hepatocellular carcinoma after argon-helium cryoablation with computed tomography perfusion.METHODS:The control group comprised 40 volunteers without liver disease.The experimental group was composed of 15 patients with hepatocellular carcinoma treated with argon-helium cryoablation.Computed tomography perfusion parameters were measured:hepatic blood flow,hepatic blood volume,mean transit time,permeability of capillary vessel surface,hepatic arterial fraction,hepatic arterial perfusion,and hepatic portal perfusion.RESULTS:After treatment,in the tumor foci,permeability of capillary vessel surface was higher,and hepatic blood flow,hepatic blood volume,hepatic arterial fraction,and hepatic arterial perfusion values were lower(P【0.05).In the liver parenchyma surrounding the tumor,hepatic arterial perfusion was significantly lower(P【0.05);however,there was no significant difference in hepatic blood flow,hepatic blood volume,mean transit time,permeability of capillary vessel surface,hepatic arterial fraction,or hepatic portal perfusion(P】0.05).CONCLUSION:Computed tomography perfusion can evaluate tumor response after argon-helium cryoablation.

Radiofrequence ablation of liver cancers

Primary and secondary malignant liver cancer are some of most common malignant tumors in the world. Chemotherapy and radiotherapy are not very effective against them. Surgical resection has been considered the only potentially curtive option, but the majority of patients are not candidates for resection because of tumor size, location near major intrahepatic blood vessels and bile ducts, precluding a margin-negative resection, cirrhotic, hepatitis virus infection or multifocial. Radiofrequence ablation (RFA), which is a new evolving effective and minimally invasive technique, can produce coagulative necrosis of malignant tumors. RFA should be used percutaneously, laparascopically, or during the open laparotomy under the guidance of ultrasound, CT scan and MRI. RFA has lots of advantages superior to other local therapies including lower complications, reduced costs and hospital stays, and the possibility of repeated treatment. In general, RFA is a safe, effective treatment for unresectable malignant liver tumors less than 7.0 cm in diameter. We review the principle, mechanism, procedures and experience with RFA for treating malignant liver tumors.

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.

Needle track seeding:A real hazard after percutaneous radiofrequency ablation for colorectal liver metastasis

Neoplastic needle track seeding following percutaneous radiofrequency ablation(RFA)of secondary liver tumors is exceedingly rare.Reports on cutaneous tumor seeding after percutaneous RFA for colorectal liver metastasis are even rarer in the literature.Here we report a case of a 46-year-old female who developed an ulcerating skin lesion along the needle track of a previous percutaneous RFA site around 6 mo after the procedure.The previous RFA was performed by the LeVeen needle for a secondary liver tumor from a primary rectal cancer.The diagnosis of secondary skin metastasis was confirmed by fine needle aspiration cytology.The lesion was successfully treated with wide local excision.We believe that tumor seeding after percutaneous RFA in our patient was possibly related to its unfavorable subcapsular location and the use of an expansion-type needle.Hence,prophylactic ablation of the needle track should be performed whenever possible.Otherwise,alternative routes of tumor ablation such as laparoscopic or open RFA should be considered.

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.

Laser ablation of liver tumors:An ancillary technique,or an alternative to radiofrequency and microwave?

Radiofrequency ablation(RFA) is currently the most popular and used ablation modality for the treatment ofnon surgical patients with primary and secondary liver tumors, but in the last years microwave ablation(MWA) is being technically improved and widely rediscovered for clinical use. Laser thermal ablation(LTA) is by far less investigated and used than RFA and MWA, but the available data on its effectiveness and safety are quite good and comparable to those of RFA and MWA. All the three hyperthermia-based ablative techniques, when performed by skilled operators, can successfully treat all liver tumors eligible for thermal ablation, and to date in most centers of interventional oncology or interventional radiology the choice of the technique usually depends on the physician's preference and experience, or technical availability. However, RFA, MWA, and LTA have peculiar advantages and limitations that can make each of them more suitable than the other ones to treat patients and tumors with different characteristics. When all the three thermal ablation techniques are available, the choice among RFA, MWA, and LTA should be guided by their advantages and disadvantages, number, size, and location of the liver nodules, and cost-saving considerations, in order to give patients the best treatment option.