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.

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.

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.

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.

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).

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.

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.

Aberration of X chromosome in liver neoplasm detected by fluorescence in situ hybridization

BACKGROUND: A diverse range of cytogenetic alterations of autosomal chromosomes has been reported to date. However, few studies have addressed the abnormalities of X chromosome in hepatocellular carcinoma (HCC) except sporadic reports on the deletion of band F1 in X chromo- some , and the clonal analysis of methylation pattern of the X chromosome-linked human androgen receptor gene. Identification of specific X chromosome alterations during the course of neoplastic development would be essential to defining the genetic basis of HCC. Therefore, we studied the regularity of aberration of X chromosome in liver canc- er. METHODS: Hepatocarcinoma cellular lines and tumor tis- sues were detected respectively through DNA probes of X chromosome after fluorescence in situ hybridization ( FI- SH). RESULTS: Increased copies of X chromosome were ob- served in all samples, and four signals of hybridization were of the major type. CONCLUSIONS: Increased copy number of X chromo- some frequently occur in liver cancer. The relationship be- tween copy number of X chromosome and liver cancer genesis needs further investigation. This study is the first of its kind determining the copy number of X chromosome in liver cancer by using FISH.

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.

Prevention of metastasis to liver by using 5-FU intraperitoneal chemotherapy in nude mice inoculated with human colonic cancer cells

AIMS Using a new approach of regional adjuvant chemotherapy to prevent cancer cells hepatic metasta- sis after radical surgery of large bowel cancer. METHODS A model of liver with metastasis of hu- man colonic cancer (HCC) cells in nude mice was used to observe the effect in prevention of metastasis of HCC cells inoculated via spleen applied with early postoper- ative intraperitoneal (IP) chemotherapy using large dose of 5-FU. RESULTS The incidence of metastasis to liver was decreased by 40%,the mean number of metastatic liv- er nodules in each animal was reduced by 50.89% and the mean survival times of each animal was prolonged by 48.21% by using 5-FU 40 mg/NS 40 ml/kg IP for two consecutive days as compared with the controls. CONCLUSIONS IP is a new and more effective re- gional adjuvant chemotheraputic approach in the pre- vention of liver metastasis HCC cells after radical surgery of large bowel cancer.

Determination of IL-2/IL-2R system in patients with liver cirrhosis.and carcinoma

AIMS To.determine the interleuking-2 and interleukin- 2 receptor (IL-2/IL-2R) system in patients with liver cirrhosis and carcinoma and compare their immune functions. The clinical significance is also discussed. METHODS Fifty patients with Liver cirrhosis (LC), 50 patients with hepatocellular carcinoma (HCC) and 30 normal controls were studied. The expression of mlL-2R was examined by immunofluorescence. IL-2's activity and serum level of soluble interleukin-2 recep- tor (sIL-2R) were measured by enzyme linked im- munosorbent assay. RESULTS IL-2's activity and the percentage of mIL- 2R expression in carcinoma were significantly lower than those in cirrhosis (P<0.01) and controls (P< 0.01),while the IL-2's activity and the expression of mlL-2R in cirrhosis were also lower than normal controls (P<0.05). The serum level of sIL-2R in carcinoma was significantly higher than that in cirrhosis (P<0.05) and controls (P<0.01),and the level in cirrhosis was higher than in controls (P<0.05). CONCLUSIONS Patients with liver cirhosis and car- cinoma share the decreased immune function of similar nature,but the latter has a more profound degree. Such resemblance in immune disturbances may be the important factor affecting the carcinogenesis of cirrhotic liver.

超声造影联合剪切波弹性成像技术对肝脏良恶性肿瘤诊断价值的Meta分析

目的 研究超声造影(CEUS)联合剪切波弹性成像(SWE)对肝脏肿瘤的诊断价值。方法 本研究根据PRISMA指南完成,PROSPERO注册号:CRD42023491288。检索Pub Med、Embase、Cochrane Library、中国知网、维普、万方数据库关于CEUS联合SWE诊断肝脏肿瘤的文献,检索时限为2000年1月—2023年10月,经筛选共纳入12篇文献,包含1 328例患者。以QUADAS-2工具对纳入的文献进行质量评估。采用Stata 15.0软件计算合并灵敏度、特异度、阳性似然比、阴性似然比、诊断比值比及异质性,绘制综合受试者工作特征曲线(SROC)并计算曲线下面积(AUC)。结果 纳入病例中,包含病灶1 457个,其中恶性病灶764个,良性病灶693个,阳性率为52.44%,阴性率为47.56%,计算得到合并灵敏度、特异度、阳性似然比、阴性似然比、诊断比值比分别为0.94(95%CI:0.91~0.96)、0.92(95%CI:0.87~0.95)、12.00(95%CI:7.40~19.40)、0.06(95%CI:0.04~0.10)、191(95%CI:87~417),异质性检验结果为Q=54.78,df=11.00,P<0.001,I2=79.92%,95%CI:69.18%~90.66%,AUC为0.98。结论 CEUS联合SWE技术对于肝脏良恶性肿瘤具有较高的诊断价值,值得临床推广使用。

Study of angiogenesis induced by metastatic and non-metastatic liver cancer by corneal micropocket model in nude mice

AIM To study the angiogenesis induced by liver cancer with different metastatic potentials using corneal micropocket model in nude mice.METHODS Corneal micropockets were created in nude mice. Tumor tissues and liver tissues were implanted into the corneal micropockets. Angiogenesis was observed using a digital camera under slit-lamp biomicroscope, and compared among different grafts and incision alone. Vascular responses were recorded in regard to the range, number and length of new blood vessels toward the grafts or incisions.RESULTS Vascular responses induced by tumor tissues were greater than those by incision alone and liver tissue grafts. LCI-D20 induced more intensive angiogenesis than LCI-D35.CONCLUSION Highly metastatic liver cancer LCI D20 was more angiogenic than low metastatic cancer LCI D35 and liver tissue. Micropocket was a useful model to study dynamic process of angiogenesis in vivo.

Methods of vascular control technique during liver resection:a comprehensive review

BACKGROUND: Significant hemorrhage together with blood transfusion increases postoperative morbidity and mortality of hepatic resection. Hepatic vascular occlusion is effective in minimizing bleeding during hepatic parenchymal transection. This article aimed to review the current role and status of various techniques of hepatic vascular occlusion during hepatic resection. DATA SOURCES: The relevant manuscripts were identified by searching MEDLINE, and PubMed for articles published between January 1980 and April 2010 using the keywords 'vascular control', 'vascular clamping', 'vascular exclusion' and 'hepatectomy'. Additional papers were identified by a manual search of the references from the key articles. RESULTS: One randomized controlled trial (RCT) and 5 RCTs showed intermittent Pringle maneuver and ischemic preconditioning followed by continuous Pringle maneuver were superior to continuous Pringle maneuver alone, respectively. Two RCTs compared the outcomes of hepatectomy with and without intermittent Pringle maneuver. One showed Pringle maneuver to be beneficial, while the other failed to show any benefit. One RCT showed that ischemic preconditioning had significantly less blood loss than using intermittent Pringle maneuver. Four RCTs evaluated the use of hemihepatic vascular occlusion. One RCT showed it had significantly less blood loss than Pringle maneuver, while the other 3 showed no significant difference. Only 1 RCT showed it had significantly less liver ischemic injury. No RCT had been carried out to assess segmental vascular occlusion. Two RCTs compared the outcomes of total hepatic vascular exclusion (THVE) and Pringle maneuver. One RCT showed THVE resulted in similar blood loss, but a higher postoperative complication. The other RCT showed less blood loss using THVE but the postoperative complication rate was similar. Both studies showed similar degree of liver ischemic injury. Only one RCT showed that selective hepatic vascular exclusion (SHVE) had less blood loss and liver ischemic injury than Pringle maneuver. CONCLUSION: Due to the great variations in these studies, it is difficult to draw a definitive conclusion on the best technique of hepatic vascular control.

Differentiation of focal liver lesions using three-dimensional ultrasonography: Retrospective and prospective studies

AIM: To differentiate focal liver lesions based on enhancement patterns using three-dimensional ultrasonography (3D US) with perflubutane-based contrast agent.METHODS: Two hundred and eighty two patients with focal liver lesions,including 168 hepatocellular carcinomas (HCCs),63 metastases,40 hemangiomas and 11 focal nodular hyperplasias (FNHs),were examined by 3D US with perflubutane-based contrast agent.Tomographic ultrasound images and sonographic angiograms were reconstructed.Among 282 lesions,enhancement patterns of 163 lesions between January 2007 and October 2007 were analyzed retrospectively.Then from November 2007 to May 2008,compared with contrast-enhanced (CE) 2D US,CE 3D US was performed on 119 lesions for prospective differential diagnosis.Sensitivity,specificity,area under receiver operating characteristic curve (Az) and inter-reader agreement were assessed.RESULTS: With the tridimensional view,dominant enhancement patterns were revealed as diffuse enhancement or peripheral ring-like enhancement,followed with washout change for HCCs or metastases,respectively,and peripheral nodular enhancement or diffuse enhancement with spoke-wheel arteries,followed by persistent enhancement for hemangiomas or FNHs,respectively.At CE 3D US,the prospective differentiation of lesions showed sensitivity 92% (mean for two readers),specificity 91% and Az value 0.95 for HCCs,84%,97%,and 0.95 for metastases,91%,98%,and 0.98 for hemangiomas and 80%,99%,and 0.99 for FNHs,respectively,while good to excellent inter-reader agreement was achieved.No significant difference exists between prospective diagnosis accuracy at CE 3D US and that at CE 2D US.CONCLUSION: CE 3D US provides a spatial perspective for liver tumor enhancement,and could help in differentiating focal liver lesions.

Study on environmental etiology of high incidence areas of liver cancer in China

INTRODUCTIONChina is a country with a high incidence of liver cancer insome areas.Liver cancer has a wide distribution andthreatens human health seriously.A rough estimationshows that out of a population of 1.2×10~8 in liver

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%.