Metastatic Liver Carcinoma Research Articles

Experience with the use of nivolumab and ipilimumab in metastatic fibrolamellar liver carcinoma

Experience with the use of nivolumab and ipilimumab in metastatic fibrolamellar liver carcinoma

Features of differential cytological diagnosis of primary and metastatic liver carcinoma.

The aim of the work was to assess the possibility of the cytological method in the diagnosis of epithelial liver tumors and to determine the cytomorphological criteria in the differential diagnosis of liver carcinomas. The authors analyzed the data of 106 fine-needle aspiration biopsies and 167 smears-prints during cor-biopsy of masses of the liver in patients who were examined at the polyclinic of the oncological dispensary in Nizhny Novgorod in 2016. - 2017 As a result, full-fledged material for cytological examination in the form of smears-prints from cor-biopsy and fine-needle aspiration biopsies was obtained in 75.4% (n=126) and 95.2% (n=101), respectively. The great possibilities of the cytological method are shown: an affirmative diagnosis of the presence of primary or metastatic liver lesions was made in 88.8% (n=112) based on smears of sorbiopsy prints and in 87.1% (n = 88) with fine-needle aspiration biopsies. Typical cytomorphological criteria for primary and metastatic liver carcinomas made it possible to determine the origin of the primary tumor in 56.6% of cases (n=98).

Lower bile duct metastasis from rectal cancer after surgery for liver metastasis and intrahepatic bile duct metastasis: a case report

BackgroundBiliary metastasis of colorectal cancer is a manifestation of metastatic liver carcinoma, and is often difficult to differentiate from cholangiocarcinoma. Further, lower bile duct metastasis of colorectal cancer is rare. We report the case of a 74-year-old woman who underwent pylorus-preserving pancreatoduodenectomy for lower bile duct metastasis of rectal cancer.Case presentationThe patient had undergone laparoscopic low anterior resection for rectal cancer (pT3N0M0 stage IIA) 6 years ago, laparoscopic anterior liver resection for liver metastasis (Couinaud segment V) 3 years ago, and left and caudal lobectomy with extrahepatic bile duct resection for left intrahepatic bile duct metastasis 6 months ago. A follow-up examination showed a 15 mm mass in the common bile duct, for which she underwent pylorus-preserving pancreatoduodenectomy. Histological and immunohistological examination of the specimens revealed similar cytokeratin (CK) expression patterns, which were negative for CK7 and positive for CK20. Therefore, the definitive diagnosis was metastasis from rectal cancer.ConclusionsIn summary, we encountered a case of lower bile duct metastasis from rectal cancer, which is often difficult to differentiate from cholangiocarcinoma. In such patients, CK7 and CK20 expression patterns are important in differentiating the two. The mechanism of metastasis in this case was considered to be through cancer cell implantation from lymphatic spread, or through distant metastasis of the primary cancer.

SUN-919 Ectopic ACTH Syndrome: An Aggressive Presentation Due to Metastatic Liver Cancer of Unknown Primary

Background: Ectopic Cushing’s Syndrome is a rare but often aggressive condition caused by ACTH-hypersecretion from non-pituitary tumors. In patients with metastatic cancer, as well as those with occult tumors, the diagnosis and management can be extremely challenging. Clinical Case: A 25-year old woman recently diagnosed with poorly differentiated metastatic liver carcinoma of unknown primary was admitted for lower extremity edema and worsening fatigue for the preceding month. Since being diagnosed with liver cancer, she developed uncontrolled hypertension, persistent severe hypokalemia and facial “puffiness”. Physical exam was remarkable for moon facies and truncal obesity but no evidence of striae. An overnight 1-mg dexamethasone suppression test resulted in an elevated morning cortisol level of 93.4 mcg/dL and elevated ACTH of 299 pg/mL. A 24-hour urine cortisol was significantly elevated at 4,448 mcg/24 hours. These findings were consistent with hypercortisolism due to hypersecretion of ACTH. An MRI of the sella revealed no pituitary abnormality. A high-dose dexamethasone suppresion test (single 8 mg dose) was performed and her morning cortisol level remained elevated at 98.6 mcg/dL, consistent with ectopic ACTH secretion. She was treated for the underlying malignancy with carboplatin and paclitaxel. After a thorough discussion of therapeutic options, she was prescribed Ketoconazole with the plan to medically control the hypercortisolism potentially followed by bilateral adrenalectomy. Ketoconazole was up-titrated and Spironolactone was added resulting in significant improvement of hypokalemia and hypertension. Unfortunately, one week after discharge she was re-admitted due to worsening performance status, watery diarrhea and abdominal pain. A serum cortisol level was elevated at 124 mcg/dL and Metyrapone was added to her regimen. Unfortunately, her performance status continued to decline due to progression of cancer and uncontrolled hypercortisolism. As a result, she was deemed a poor surgical candidate for bilateral adrenalectomy. The patient’s condition rapidly deteriorated and she developed malignant ascites as well as altered mental status. In accordance with her wishes, a DNR order was placed and she passed away shortly thereafter. Conclusion: Ectopic ACTH-syndrome is the etiology of 10–20% of cases of Cushing’s syndrome. Clinical presentation is often sudden and rapidly progressive. Severe hypertension and hypokalemia are seen more commonly than in Cushing’s disease. Cases secondary to occult tumors or metastatic cancer can be particularly challenging to treat when it is not possible to eliminate the source of ACTH hypersecretion via surgical or medical treatment. In patients such as this, early bilateral adrenalectomy should be considered after starting medical therapy in order to reduce morbidity and mortality due to hypercortisolism.

The chemokine CCL7 regulates invadopodia maturation and MMP-9 mediated collagen degradation in liver-metastatic carcinoma cells.

Liver metastases remain a major cause of death from gastrointestinal tract cancers and other malignancies, such as breast and lung carcinomas. Understanding the underlying biology is essential for the design of effective therapies. We previously identified the chemokine CCL7 and its receptor CCR3 as critical mediators of invasion and metastasis in lung and colon carcinoma cells. Here we show that the CCL7/CCR3 axis regulates a late stage in invadopodia genesis namely, the targeting of MMP-9 to the invadopodia complex, thereby promoting invadopodia maturation and collagen degradation. We show that this process could be blocked by overexpression of a dominant negative RhoA in highly invasive cells, while a constitutively active RhoA upregulated invadopodia maturation in CCL7-silenced and poorly invasive and metastatic cells and also enhanced their metastatic potential in vivo, collectively, implicating RhoA activation in signaling downstream of CCL7. Blockade of the ERK or PI3K pathways by chemical inhibitors also inhibited invadopodia formation, but affected the initiation stage of invadopodia genesis. Our data implicate CCL7/CCR3 signaling in invadopodia maturation and suggest that chemokine signaling acts in concert with extracellular matrix-initiated signals to promote invasion and liver metastasis.

The significance of arginase-1 expression in the diagnosis of liver cancer: A protocol for a systematic review.

Background:Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Pathologic distinction between HCC and intrahepatic cholangiocarcinoma (ICC) and metastatic adenocarcinoma can be challenging and sometimes requires immunohistochemical panels. Recently, arginase-1 (ARG-1) has been introduced for differentiation of these tumors.Methods:We will search Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure through August 1, 2019, comprehensive collection studies about the diagnostic value of ARG-1 for HCC. Two reviewers will screen literature according to the inclusion and exclusion criteria, extract data, and assess the quality of included studies. Review Manager 5.3 and STATA 15.0 will be used to conduct the meta-analysis.Results:The review will provide a high-quality synthesis of current evidence of the diagnostic value of liver cancer. The results will be published in a peer-reviewed journal.Conclusion:We hope that the results of this study will provide significant evidence to assess the value of ARG-1 in differential diagnosis of HCC, ICC, and metastatic carcinoma of liver.

Mouse models for human colorectal cancer with liver metastasis

Objective: To established Apc(loxp/loxp)+Kras(LSL-G12D/-)+Smad4(loxp/loxp) transgenic mouse model that mimick the occurrence and development of human sporadic colorectal cancer(CRC) and its liver metastasis. Methods: C57BL/6-Apc(tm1Tyj)/J(Apc(loxP)), B6.129S4-Kras(tm4Tyj)/J(Kras(LSL-G12D)), 129S6-Smad4(tm2.1Cxd)/J(Smad4(loxP)) and C57BL/6J mice were crossed, and genotype with Apc(loxP/loxP)+Kras(LSL-G12D/-)and Apc(loxP/loxP)+Kras(LSL-G12D/-)+Smad4(loxP/loxP)were generated. Genotypes of the mice were identified by PCR and real-time quantitative PCR. The mice were divided into Apc(loxP/loxP)+Kras(LSL-G12D/-)+Smad4(loxP/loxP) group (n=20) and Apc(loxP/loxP)+Kras(LSL-G12D/-)group(n=24). Lentivirus expressing Cre enzyme and IRES-luciferase were injected into the submucosa of colon or rectum of the transgenic mice under colonoscopy. Intraabdominal injection of D-luciferase into mice every 4 weeks, imaging with small animal in vivo imaging system(IVIS). The tumor size, tumorigenesis rate and metastasis ratio were analyzed. At the end of the 20th week, the colorectal lesions and metastatic tissues of mice were stained with hematoxylin-eosin(HE) and the pathological changes were observed under microscope. Results: Apc(loxp/loxp)+Kras(LSL-G12D/-)+Smad4(loxp/loxp) and Apc(loxp/loxp)+Kras(LSL-G12D/-)transgenic mice were successfully bred. The colorectal stem cells of the transgenic mouse mutated leading tumor lesion and liver metastatic under the induction of Lentivirus(Cre-IRES-luciferase). The primary and metastatic foci of colorectal carcinoma and liver metastasis in mice were proved to be adenocarcinoma and liver metastatic carcinoma by histopathological examination. The primary tumor size inApc(loxP/loxP)+Kras(LSL-G12D/-)+Smad4(loxP/loxP) group and Apc(loxP/loxP)+Kras(LSL-G12D/-)group was(3.52±0.26) and(3.45±0.20)mm, respectively,without significant difference(t=0.872, P=0.388).The tumorigenesis rate was 70.0% and 50.0% respectively, and there was no significant difference between the two groups(χ(2)=0.440, P=0.507). The metastasis rate of two groups were 58.3% and 8.3%respectively(Fisher's exact test, P=0.027). Conclusions: In this study, the colorectal carcinogenesis and its spontaneously metastasis to the liver of CRC were induced by Lentivirus(Cre-IRES-luciferase) in our established transgenic mice,which successfully simulated the occurrence and development of human sporadic CRC and its liver metastasis.

Significant clinical response of advanced colorectal cancer to combination therapy involving capecitabine and adoptive cell transfer therapy: a case report

Significant clinical response was obtained in a patient with stage IV colorectal cancer (CRC) following combination therapy involving capecitabine and adoptive cell transfer therapy. She had laparoscopic lower anterior resection and left liver metastatic carcinoma resecting in 20th, February, 2017. Capecitabine was used to further treatment for an unresectable hepatic metastasis. The serum level of carcinoembryonic antigen (CEA) was increased significantly after dropped temporarily. Since then, the patient took the adoptive cell transfer therapy at the same time. αβT cells and NK cells were injected intravenously into the patient. After the first transfusion with αβT cells, the tumor biomarker, CEA, dropped obviously from 14.7 to 6.1 ng/mL. And it came to 1.9 ng/mL after four times treatment, which was back into normal range (<5 ng/mL). Flow cytometry (FCM) was used to reveal the detailed immunological status of this patient before and after adoptive cell transfer therapy. With 19-month follow-up, neither recurrence or complication was founded. Combination therapy involving adoptive immunotherapy and capecitabine may be the potential method for advanced CRC with less complication.

Establishment of metastatic liver carcinoma model by implanting AX7 cells into rabbit liver, and its histological findings.

Background: Progression of metastatic liver carcinoma from any original cancer is aggressive and the prognosis is very poor. Therefore the new model that is easily approachable to study the propagation and prognosis of metastatic liver carcinoma is necessary. The aim of this study is to confirm the tumor formation and metastatic activity of anaplastic thyroid cancer and to support the research basis for the next generation cancer treatment that is to be developed, by carrying out additional experiments like cytokine stimulation. We investigated sequential findings of immunohistochemistry of rabbit hepatic malignancy induced by AX7 cells.Methods: 13 rabbits implanted with AX7 cells directly into liver parenchyme with laparotomy were investigated by histopathology examination, immunohistochemistry, which is useful for the evaluation of metastatic cancer angiogenesis. Growing tissue at the edge of the mass was collected and placed in the petri dish filled with saline. After removing necrotic and fibrous tissue, tumor tissue was cut into pieces, placed in saline, and extracted during the experiment.Results: Tumor growth and malignancy was confirmed on the 10th day after AX7 cells were implanted into liver. Positive for VEGF staining was found in the cytoplasm or cell membrane. The scores for VEGF stained cells were moderately positive (++) on day 10, strongly positive (+++) on day 44. Ki-67-positive hepatocytes reached at 65% on day 10, at 65.78% on day 14, at 66.4% on day 30, at 67.88% on day 44.Conclusion: AX7 cells implanted into liver can be used as a new rabbit metastatic liver carcinoma model and would become useful for human metastatic liver carcinoma studies. Future studies may facilitate the establishment of an effective systemic therapy for the metastatic liver cancer.

Early experience of laparoscopic liver resection: A single institution experience with 37 consecutive cases.

Backgrounds/AimsLaparoscopic liver resection (LLR) has evolved and broadened in scope. While open liver resections are currently being performed safely in our hospital, LLRs are being implemented in fewer cases. The aim of this study was to review our initial experience in LLR to assess early outcomes of the procedure.MethodsA retrospective chart review was conducted for 37 patients who underwent laparoscopic liver resections for various indications between January 2014 and July 2017 by a single surgeon who had performed 161 open liver resections and 50 live donor hepatectomies during the same period.ResultsOf 37 laparoscopic liver resections performed, male to female ratio was 23 to 4. Their mean age was 61.4 years. There were 13 cases of wedge resections, 7 cases of left lateral sectionectomy, 9 cases of left hepatectomy, and 8 cases of right hepatectomy. Pathology included hepatocellular carcinoma (n=20), cholangiocarcinoma (n=3), intrahepatic duct stones (n=6), metastatic liver carcinoma (n=6), primary neuroendocrine tumor of liver (n=1), and huge hemangioma (n=1). The mean operation time was 174.7 minutes (range, 40–410 minutes). Mean blood loss was 200.5 ml (range, 10–2200 ml). There were no open-conversion cases. There were no intraoperative or postoperative complications except that a case of severe portal vein stenosis in the laparoscopic right hepatectomy occurred postoperatively. The patient underwent reoperation (portal vein resection and anastomosis, stenting). The mean hospital stay was 8.7 days (range, 2–44 days).ConclusionsEven though our experience in laparoscopic liver resection is still developing, our results are comparable to those of other studies. Therefore, an experienced surgeon in performing open liver resection should be able to perform the laparoscopic liver resection safely.

Microwave ablation of hepatic malignant tumors using 1.5T MRI guidance and monitoring: feasibility and preliminary clinical experience

Purpose: To evaluate the feasibility and therapeutic efficacy of 1.5-T MRI-guided and monitored microwave ablation in patients with hepatic malignant tumors.Materials and Methods: This retrospective study was approved by the ethics committee of the First Affiliated Hospital of Fujian Medical University. Thirty-five patients (32 men, three women) with 48 lesions (maximum diameter < 3 cm) underwent microwave ablation under the guidance and monitoring of a 1.5-T MRI. The MRI-compatible microwave generator was appended with a magnetic shield case, and the cable was combined with a choke coil for shielding the Larmor processing frequency. The average age of the patients was 56.51 ± 11.36 years (31–77 years). Twenty-eight patients (37 lesions) displayed hepatocellular carcinoma and seven patients (11 lesions) had metastatic liver carcinoma. The mean maximum tumor diameter was 12.31 ± 4.72 mm (range 5.0–25.7 mm).Results: MRI scans were performed simultaneously without electromagnetic interference during ablation. The average maximum diameter of the hypointense zone of the last monitored T2WI sequence, hypointense zone of post-procedure T2WI sequence, and hyperintense zone of post-procedure T1WI were 28.82 ± 7.58 mm, 29.79 ± 7.91 mm, and 28.28 ± 8.37 mm, respectively, with no observed statistical difference (F = 0.434, p = .649). The technical success rate was 100%. The average follow-up duration was 11.43 ± 5.29 (4–33) months. The technique efficacy rate was 100%.Conclusion: MRI-guided and monitored microwave ablation of hepatic malignant tumors is feasible and potentially safe and effective.Key pointsMRI-guided microwave ablation of hepatic malignant tumors is feasible.The MRI monitoring scan could accurately reflect the scope of ablation lesion.On T1WI, the ablation lesions of liver showed the ‘target sign’.

Useful Application of Immunostaining to Malignant Pleural Effusion among Lao People in Vientiane Capital, Lao PDR

Background:Pathology and laboratory medicine (PALM) services are limited in low-resource countries, such as Lao PDR. Patients with malignant pleural effusion (MPE) are not properly diagnosed and treated in these situations. The purpose of this study is to confirm the usefulness of immunocytochemistry in MPE to identify the histological type and probable primary site of cancer of MPE and to discuss its usefulness in low-resource countries, such as Laos.Methods:We retrospectively reviewed glass slides of pleural effusion sent to the Department of Pathology at the University of Health Sciences from the central hospitals for cytological screening from January 2012 to December 2016. The cytological review, cell transfer and immunocytochemical staining were performed at Tokyo Medical and Dental University. Among 81 cases of MPE from Laos, 66 cases of malignant tumors that contained enough tumor cells were included in this study, and the slides were screened with 14 primary antibodies to classify the histological type and identify the probable primary site of carcinoma.Results:Among the 66 cases, 34 cases (52%) were of female patients, and 32 cases (48%) were of male patients. The patients’ ages ranged from 28 to 88 years with an average of 58 years. The immunocytochemical study identified 32 cases (49%) of primary lung adenocarcinoma, two cases (3%) of malignant mesothelioma, one case (1.5%) of breast/gynecological carcinoma, one case (1.5%) of T cell lymphoma, and one case (1.5%) of B cell lymphoma. Twenty-nine cases (43.5%) were classified as carcinoma not otherwise specified. Pulmonary small cell carcinoma/squamous cell carcinoma and metastatic colon, prostate, and liver carcinoma were not identified among the cases.Conclusions:Immunocytochemistry is a useful ancillary method in MPE diagnostics. This method could be applied in the pathological laboratories in low- or middle-resource countries, such as Laos.

Towards Liver SBRT – A clinical experience

Historically external beam radiation therapy has not been used to treat metastatic liver and hepatocellular carcinoma (HCC), due to the increased risk of radiation induced liver disease (RILD). Remarkable advances in imaging and delivery technology can now be harnessed to enhance target localisation and local control for patients suffering with HCC and oligometastatic liver disease. Image-Guided Radiation Therapy (IGRT) and Stereotactic Body Radiation Therapy (SBRT) are rapidly revolutionising the planning and delivery of radiation therapy in the treatment of cancer. Being able to see and track the changes that take place over a radical course of radiation therapy present numerous exciting opportunities. The treatment of liver carcinoma with radiotherapy is a highly complex non-invasive treatment option that can deliver significant benefits to non-operable patients when administered successfully. Safe administration of the world’s most advanced radiotherapy treatment techniques such as 4D-IGRT or end expiration breath-hold (EEBH), flattening filter free (FFF), SBRT volumetric arc therapy (VMAT) is a highly challenging commitment and endeavour to undertake, especially so for the clinical physicist. This presentation will highlight some of the main challenges encountered when developing and implementing a liver SBRT program across a multi-disciplinary team, which includes education and training, patient selection, physics QA and establishing process-specific documentation.

Novel navigation system by augmented reality technology using a tablet PC for hepatobiliary and pancreatic surgery.

We previously developed an image-guided navigation system (IG-NS) using augmented reality technology for hepatobiliary and pancreatic (HBP) surgery. This system superimposed a 3D model onto a stereoscope-captured surgical field (i.e., the scope method). Unfortunately, this method requires an expensive stereoscope, surgeons have to shift their eyesight away from the surgical field, and the method has poor controllability. Therefore, an IG-NS using a tablet PC (i.e., the tablet method) was developed. The aim of the current study is to evaluate the efficiency of this novel method. We studied 9 patients, for whom a 3D model was created from computed tomography images. After registration was performed, the 3D model was superimposed onto the surgical field, which was captured by the tablet PC's camera. The IG-NS could be applied with very little time lag. The visibility and controllability of the tablet method were superior to those of the scope method. It was especially useful in surgery for multiple metastatic liver carcinoma due to easy localization of the position of the carcinomas and vessels. We successfully developed the tablet method and tested it in a clinical setting. This system may contribute to surgical efficacy and improve the educational effects.

A33 shows similar sensitivity to but is more specific than CDX2 as an immunomarker of colorectal carcinoma.

CDX2 is widely used as a sensitive and specific immunomarker for colorectal carcinoma (CRC), but neither its sensitivity nor its specificity is absolute. The aim of this study was to compare CDX1 and A33 with CDX2 as immunomarkers for CRC. As a pilot study, whole sections of 51 cases of liver metastatic carcinoma with different origins-colorectum (n = 32), breast (n = 3), oesophagogastric tract (n = 4), lung (n = 3), pancreas (n = 8), and prostate (n = 1)-were immunostained with CDX1, CDX2, and A33. A33 showed higher sensitivity as a CRC immunomarker, greater interobserver reproducibility for assessment of expression and less background cross-reactivity than CDX1. Therefore, only A33 was compared with CDX2 for a tissue microarray (TMA)-based study of primary adenocarcinomas with different origins: CRC (n = 55), liver deposits of metastatic CRC (n = 60), breast (n = 101), lung (n = 40), oesophagogastric tract (n = 134), ovary (n = 67), pancreas (n = 77), and prostate (n = 56). When the whole section and TMA cases of CRC were combined, A33 had a sensitivity of 95.9% and CDX2 had a sensitivity of 97.2%. When the whole section and TMA cases of non-colorectal carcinomas were combined, A33 had a specificity of 85.4% as a marker of CRC and CDX2 had a specificity of 64.3%. The higher specificity of A33 than of CDX2 as a CRC immunomarker was particularly seen among pancreatic and ovarian carcinomas. Furthermore, unlike what was seen with CDX2, none of the prostatic and lung carcinomas studied showed A33 positivity. A33 shows similar sensitivity to but is more specific than CDX2 as an immunomarker of CRC.

Application of indocyanine green-fluorescent imaging technique in planning resection line and real-time surgical navigation in small hepatocellular carcinoma

Objective: To explore the value of near-infrared technology guided by indolecyanine green(ICG) in planning resection line and real-time surgical navigation in small liver cancer. Methods: From March to September 2015, 11 patients with hepatic tumors received hepatectomy were treated in First Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University.There were 5 male and 6 female patients with average age of (55±10)years (range 39-70 years). Among whom, there were 9 cases with hepatocellular carcinoma and 2 cases with colorectal cancer. A near-infrared light camera system was used to detect the liver surfaces before resection, and to plan resection line and surgical specimens. A student's t test was used to compare continuous parametric variables. Results: The ICG-fluorescent imaging and histological examination had been used in the 15 lesions of the 11 patients. Among the 15 lesions, 7 lesions were detected by visual inspections, palpation and ICG-fluorescent imaging, 6 lesions were identified only by ICG-fluorescent imaging, 2 lesions were detected only by ICG-fluorescent imaging after resection.Results of pathologic examination indicated that the total fluorescent type include 5 well differentiated hepatocellular carcinoma and 2 cirrhotic nodule; the partial fluorescent type include 3 moderately differentiated hepatocellular carcinomas and 1 well differentiated hepatocellular carcinomas; the rim fluorescent type included 2 liver metastatic carcinoma and 2 poorly differentiated hepatocellular carcinomas. The average diameter of the tumor size measured by CT was (1.7±0.2)cm, while the average diameter measured by ICG-fluorescent imaging was (1.7±0.3)cm(t=-0.188, P>0.05). Conclusion: Near-infrared technology guided by ICG has important value in planning resection line and real-time surgical navigation in small liver cancer.

The diagnostic value of pCEA, mCEA, AFP and CK19 in differentiating primary and metastatic carcinoma of liver

GIRIŞ ve AMAC: Hepatoselluler karsinom HCC hepatositlerden koken alan ya da hepatoselluler diferansiyasyon gosteren, primer karaciger tumorlerinin %80-85’ini olusturan malign tumordur. Karacigerin primer ve metastatik malign tumorlerinin ayirici tanisinda ozellikle tru–cut biopsilerde tanisal guclukle karsilasilmaktadir. Karaciger, metastatik karsinomlarin en fazla izlendigi organ olmasi nedeni ile bu ayrimin kesin bir sekilde yapilmasi onem kazanmaktadir. Bu calismada, klinik ve radyolojik bulgular esliginde histopatolojik olarak tani almis primer HCC, kolanjioselluler karsinoma KCC ve metastatik adenokarsinomlarda immunohistokimyasal CK19, AFP, mCEA ve pCEA’nin boyanma profilleri arastirilmistir.YONTEM ve GERECLER: 39 hepatoselluler karsinom, 33 metastatik adenokarsinom ve 3 KCC ait olmak uzere toplam 75 olgunun 15 mm’den buyuk igne biyopsileri ve wedge rezeksiyon materyalleri calismaya dahil edildi. Olgulara immunhistokimyasal olarak pCEA, mCEA, AFP ve CK19 uygulandi.BULGULAR: 39 HCC olgusunun yas ortalamasi 49,5 15-75 tespit edilmis olup, erkek/kadin orani 3,8: 1 dir. HCC olgularinin 6’si grade I %15.2 , 22’si grade II %56.4 , 9’u grade III %23 , 2’si grade IV %5.4 idi. Uc KCC olgumuzda yas ortalamasi 44 olup, 3’u de erkektir. Uc olguda da AFP’nin negatif olmasi dikkat cekicidir. 33 metastatik karaciger tumorunun kadin/erkek orani 1: 1dir. Yas ortalamasi 54.2 37-74 idir. CK19, 23 %60.6 olguda pozitif olarak bulunmustur. Pankreas ve safra kesesi kaynakli metastatik tumorlerin hepsinde yaygin pozitiflik saptanmistir.TARTIŞMA ve SONUC: CK19, HCC ve KCC ayirici tanisinda onemli bir belirleyiciyken metastatik adenokarsinom ve KCC ayriminda yardimci degildir. pCEA’nin HCC’lerde kanalikuler tipte boyanmasi HCC’ye ozgu bir boyanma olarak metastatik adenokarsinomlardan ayriminda onemlidir. mCEA ise metastatik adenokarsinomlarda kuvvetli intrasitoplazmik ekspresyon gosterdiginden HCC ve metastaz ayriminda yardimci bir markerdir. AFP ekspresyonunun spesifite ve sensitivitesi dusuk oldugundan metastaz ve HCC ayirici tanisinda cok faydali degildir.

Imaging features and diagnosis of hepatic cystic echinococcosis

Objective To summarize the features of computed tomography (CT) and magnetic resonance imaging (MRI) of hepatic cystic echinococcosis, and investigate the key points of identification and diagnosis. Methods The clinical data of 58 patients with hepatic cystic echinococcosis who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from August 2011 to August 2014 were retrospectively analyzed. Patients received plain and enhanced scan of CT and MRI. Hepatic cystic echinococcosis was divided into the 5 types according to the literatures, including unilocular echinococcasis in type Ⅰ, multivesicular hydatid cysts in type Ⅱ, anechoic content with detachment of laminated membrane from the cyst wall in type Ⅲ, calcification of lesions in type Ⅳ and mixed echinococcosis in type Ⅴ. Patients who were diagnosed as with definite or suspected hepatic cystic echinococcosis underwent surgery. The follow-up including observing the recurrence of hepatic cystic echinococcosis was performed by outpatient examination and telephone interview at postoperative month 3, 6, 12 for 1 year and then once every year up to August 2015, and was ended if there was no recurrence for more than 5 years. Results (1) The results of CT and MRI examinations: of the 58 patients, 54 received scan of CT and 21 received scan of MRI. Seventeen patients were detected in type I with clear-boundary and low-density cystic lesions by CT examination; MRI examinations showed there were single or multiple, round or oval abnormal signal including low T1WI signal, high T2WI signal and low T1WI and T2WI signal of cyst wall. Thirteen patients were detected in type Ⅱ, CT examination showed the daughter cysts of multiple sizes were found in the mother cyst, arranged in honeycomb or wheel shape; MRI examination showed there were lower T1WI signal in the daughter cyst and higher T2WI signal in the daughter cyst compared with signal in the mother cyst, and low signal in the cyst wall of the daughter cyst and mother cyst. Six patients were detected in type III with in sign and water snake sign by CT examination and ribbon sign by MRI examination. Thirteen patients were detected in type Ⅳ, CT examination showed there were irregular high-density calcified shadow with the performances for return or sample volume skins changes. Nine patients in type Ⅴ had more than 2 kinds of lesions. (2) Diagnosis: 4 patients were misdiagnosed by CT examination including 3 with preoperative diagnosis of hepatic cyst and 1 with preoperative diagnosis of metastatic carcinoma of liver, with an accurate rate of diagnosis of 92.6%(50/54). Two patients with preoperative diagnosis of hepatic cystic adenocarcinoma were misdiagnosed by MRI examination, with an accurate rate of diagnosis of 90.5%(19/21). (3) Treatment and follow-up: 58 patients underwent surgery, including 40 undergoing internal capsule removal with external capsule suturing (31 with open operation and 9 with laparoscopic operation), 10 undergoing partial hepatectomy and 8 undergoing external capsule enucleation. Of 58 patients, 3 were complicated with effusion of residual cavity, 2 with unclosed external capsule, 1 with bile leakage and then was cured after 4-8 week drainage. Fifty patients were followed up for 12.0-48.0 months with a median time of 27.1 months and a follow-up rate of 86.2%(50/58). During the follow-up, 1 patient undergoing internal capsule removal had recurrence at postoperative month 8 and was cured by CT-guided interventional therapy using absolute alcohol, and other patients had no recurrence. Conclusions There was a higher accuracy in CT and MRI examinations for hepatic cystic echinococcosis. Honeycomb and wheel shapes are characteristic findings of hepatic cystic echinococcosis in type II. The characteristic performances of CT examination for hepatic cystic echinococcosis in type III are in capsule and water snake signs, and characteristic performances of MRI examination is ribbon sign. The ring-like enhancement of edge by MRI examination is an essential of identification and diagnosis between hepatic cystic echinococcosis and hepatic cyst, and irregular calcification is a differential point between hepatic echinococcosis and hepatic tumor. Key words: Echinococcosis, hepatic; Tomography, X-ray computed; Magnetic resonance imaging; Diagnosis

Imaging characteristics of hepatic epithelioid hemangioendothelioma

Objective To summarize the imaging characteristics of the hepatic epithelioid hemangioendothelioma (EHE). Methods The clinical data of 6 patients with hepatic EHE who were admitted to the Yantaishan Hospital (3 patients), Zhangzhou Hospital of Traditional Chinese Medicine (2 patients) and Zhangqiu Hospital of Traditional Chinese Medicine (1 patient) between March 2007 and June 2014 were retrospectively analyzed. All the patients underwent plain scan and dynamic enhanced scan of computed tomography (CT), and the number, shape, size, location, density or signal, level and method of enhancement of the lesions were observed and analyzed. Six patients were followed up by outpatient imaging examination up to June 2014, and the changes of lesions were observed. Results Among the 6 patients, 1 solitary lesion and 5 multiple lesions were detected, and the total lesions were 125 including 1 patient with 75 lesions. The lesions were round or round-like and originated commonly from the right lobe of liver and hepatic subcapsular with a maximum diameter of 0.5-3.5 cm. Plain scan of CT showed that the lesions in 6 patients had low density with the clear boundary. MRI showed that low T1WI signal and high or slightly high T2WI signal of the lesions were detected in 4 patients. Two patients had liver capsular retraction sign. The ring-like enhancement of 1 lesion and homogeneous enhancement of 5 lesions were found by dynamic enhanced scan of CT in 6 patients and enhanced scan of MRI in 4 patients. Enhanced signal in all the lesions was detected in the delayed phase. Veins into or through lesions were found in 3 lesions, with normal or narrowing vascular cavity. One patient had visible lollipop sign. Of the 6 patients, 5 were confirmed as with metastatic carcinoma of liver, and 1 was suggested as with cholangiocarcinoma. Six patients were diagnosed with hepatic EHE by pathological examination using hepatic biopsy technique. Among the 2 patients with hepatic EHE who didn't receive antineoplastic treatment after the diagnosis, 1 patient received CT examination at year 2 after first visit, which showed capsular retraction sign, and then was diagnosed as with secondary hepatic cirrhosis by MRI at 4 years after first visit. Another patient was diagnosed as with hepatic cirrhosis by CT examination at year 6.5 after first visit. One patient was diagnosed with tumor recurrence of hepatic left lobe by CT reexamination at postoperative year 4, and underwent ultrasound-guided radio frequency ablation (RFA) treatment based on no enlargement of tumor during 1-year follow-up, and then returned a normal condition after half year follow-up. Other 3 patients undergoing operation were followed up at postoperative year 1 , 4, 5 with no recurrence and metastasis. Conclusions Intrahepatic single or multiple nodules and delayed reinforcement by dynamic enhanced scan of CT and MRI are the typical imaging performances of hepatic EHE. There are certain characteristics in the liver the lollipop sign, capsular retraction sign and veins into or through the lesions. Mutual fusion and fibrosis of lesions leading ultimately to secondary liver cirrhosis may be characteristics of EHE growth. Key words: Liver neoplasms; Epithelioid hemangioendothelioma; Tomography, X-ray computed; Magnetic resonance imaging

Diagnostic Value of Arginase-1 and Glypican-3 in Differential Diagnosis of Hepatocellular Carcinoma, Cholangiocarcinoma and Metastatic Carcinoma of Liver.

Background:Hepatocellular carcinoma is the most common primary liver cancer. Pathologic distinction between Hepatocellular Carcinoma (HCC) and adenocarcinoma (Cholangiocarcinoma (CC) and Metastatic Adenocarcinoma (MA)) can be challenging and sometimes requires immunohistochemical panels. Recently, Arginase-1 (ARG-1) and Glypican-3 (GPC-3) have been introduced for differentiation of these tumors.Objectives:The aim of this study was to determine the diagnostic accuracy of ARG-1 and GLP-3 in differential diagnosis of liver tumors.Patients and Methods:Eighty-nine formalin-fixed paraffin-embedded tissue blocks including 43 cases of documented HCCs, 19 cases of documented CC, and 27 cases of MA involving the liver (15 colon, 5 stomach, 3 pancreas, 2 gallbladder, 1 duodenum and 1 ampulla of vater) were evaluated for immunohistochemical expression of ARG-1 and GPC-3.Results:Arginase-1 and GPC-3 demonstrated diffuse staining, as reactivity in > 97% of HCCs, whereas only one (5.3%) and 2 (10.5%) of 19 CC cases show positive staining for GPC-3 and ARG-1, respectively. The expression of both markers in MA showed 6 (22.2%) for ARG-1 and 3 (11.1%) for GPC-3, especially with colorectal origin. Our findings showed a statistically significant difference between ARG-1 and GPC-3 expression in HCC, CC and MA.Conclusions:The findings of this study reveal that both ARG-1 and GPC-3 are helpful IHC markers to separate HCC from CC and MA. Furthermore, ARG-1 shows 100% sensitivity and 82.6% specificity for the diagnosis of HCC whereas GPC-3 demonstrated 97.7% sensitivity and 91.3% specificity for the diagnosis of this tumor.