Cellular Immune Function In Patients With Hepatocellular Carcinoma (hcc) And The Diagnosis And Differential Diagnosis Of Liver Rare Placeholder

Background and ObjectivePARTIThe immune system of the patients with malignant tumors, such as liver cancer, is often unbalanced. This imbalance mainly manifests the inhibition of the cellular immune function, which shows the reduction in the number of T lymphocytes in peripheral blood or or the inhibition of function of these cells. Therefore, it is of important clinical significance to research the cellular immune function of the patients with hepatocellular carcinoma. This is helpful to understand the change of immune status of the patients and the diagnosis and treatment of HCC. The human immune system is one of the most complex human systems. There are great varieties of immune cells, especially lymphocytes. The occurrence, development and apoptosis of different cell and immune status are in the dynamic changes all the time.Studying only one lymphocyte subset is totally inadequate to show the body’s immune status. This part aims to study the correlativity of the prognosis of the patients with HCC and lymphocyte subsets as well as the differences among lymphocyte subsets, especially T-cell subsets, of the patients in various disease states.PART IINo.1:Inflammatory myofibroblastic tumor of the liver (IMTL) is a very rare benign disease with a good prognosis. The aim of the current study was to determine the clinical, radiological, and pathological characteristics of IMTL. The diagnosis and treatment strategies were discussed; No.2:Intrahepatic biliary cystadenocarcinomas and cystadenomas share similar radiological and clinicopathological features, and the differential diagnosis is difficult. Our study aims to give a tactics to differ intrahepatic bilibary cystadenomas from cystadenocarcinomas in diagnosis; No.3:To discussed the abscess type of primary liver cancer (presented as liver abscess) for the purpose of the early diagnosis and treatment.Methods PARTIAdult patients were chosen who admitted in the liver surgery department of Peking Union Medical College Hospital from January2009to April2010. These patients were not consolidated with immune diseases and taking any immunosuppressive agents. These patients were divided into five groups:HCC undergoing surgery Group (43cases), HCC undergoing no surgery Group (24cases) IHCC Group (4cases), Cirrhosis Group (3cases) and hepatic hemangioma Group (4cases). Data on laboratory tests, history, symptoms and signs of the patients were collected. Lymphocyte subsets of patients with hepatocellular carcinoma, bile duct carcinoma patients, cirrhosis and hemangioma,were detected by flow cytometry and compared between different groups.PART IINo.1:A total of eleven patients with pathologically confirmed IMTL receiving treatment at Peking Union Medical College Hospital over a15-year period were reviewed retrospectively. The analysis included demographics information and pertinent clinical data. Results were compared that obtained from patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHCC) and, metastatic liver cancer (MLC) receiving surgical resetion. No.2:Patients with a pathological diagnosis of cystadenocarcinomas and hepatobiliary cystadenomas were retrospectively reviewed from January1991to July2012; No.3:Patients presenting as with a pathological diagnosis of primary liver cancer (PLC) were retrospectively reviewed from January2009to August2012.ResultsPARTI43patients,36males and7females were enrolled into the HCC operation group. The mean age was56.5±12.1years.14patients had died until the end of the follow-up, while24cases survived.2patients died in3months after surgery, accounting for4.7%. The one-year and two-year survival rate were62.8%,34.9%, respectively. The overall survival time was18.8±8.4months. The serum AFP of death sub-group was higher than that of non-death sub-group (P=0.030). The number of tumor thrombus of the patients in death sub-group was more (P=0.001). Univariate analysis showed:tumor thrombus (P=0.000), AFP (P=0.035), WBC (P=0.010), the LY proportion (P=0.010), the Neut count (P=0.018), the Neut proportion (P=0.019), plt (P=0.013), and CD4+CD45RA+proportion (P=0.026) were risk factors of death for the patients with HCC after surgery. Multivariate analysis showed that:AFP (P=0.015) and tumor thrombus (P=0.001) were the independent risk factors of death for those patients. CD4+T cells innocence subsets (CD4+CD45RA+T cells) proportion of the death sub-group of death was significantly higher than that of the non-death sub-group(P=0.029). The average count of T lymphocytes (CD3+) of the patients in HCC surgery group was higher than of patients in HCC non-surgery group, respectively (P=0.001), as well as the average count CD3+CD8+T cells (P=0.020), the proportion of CD4+T cells in T cells (P=0.008) and CD4+CD28+T-cell count (P=0.012). There was no statistically significant difference of CD4/CD8between the two groups (P=0.194). The proportion of regulatory T cells (CD4+CD25+CD127" T cells) in peripheral blood of HCC surgery patients were2.94%±1.72%, there was no significant difference among each groups (P=0.492).PART IINo.1:In comparison to HCC, IHCC, and MLC, IMTL has an earlier onset (P＜0.001). IMTL patients had significantly lower AST (P=0.003) and higher ALP (P=0.034) than HCC patients, and higher GGT (P=0.010) than MLC patients. Increased serum alpha-fetoprotein (AFP) level was detected in only one out of the11IMTL patients (98.78ng/ml). Serum AFP was significantly lower in patients with IMTL (P=0.000) than in those with HCC but not IHCC (P=0.558) or MLC (P=0.514). In contrast to elevated serum CA19-9in patients with HCC/IHCC/MLC, the serum CA19-9in IMTL cases was generally within the normal range (vs. HCC P=0.008; vs. IHCC P=0.000; vs. MLC P=0.022). In9IMTL patients, the tumor appeared as a hypoechogenic solid mass on the ultrasonography. In contrast, most patients with HCC, IHCC, or MLC showed hybrid echo. In contrast CT and MRI, the lesion of IMTL and MLC appeared as peripheral enhancement.No.2:Thirty-nine patients had pathologically diagnosed Intrahepatic biliary cystadenocarcinomas (15/39,10males and5females, mean age:57.93±14.39years) or cystadenomas (24/33,4males and20females, mean age:43.75±12.51years). Significant differences were both shown in age (P=0.002) and gender (P=0.002) between Intrahepatic biliary cystadenocarcinoma and cystadenoma. There were no significant differences in symptom, symptom duration, CA199and CEA. In the cystadenocarcinoma group, the lesions of14cases located only in the left lobe of the liver, while16cases in the cystadenoma group (P=0.115). The maximum diameter of the tumors were7.38±3.98cm and10.21±7.82cm (P=0.293), respectively.5(5/11) Cystadenocarcinoma patients were combined with with introhepatic biliary dilatation nearby the lesions, while only1cystadenoma patient (1/21)(P=0.011) had the feature. Other imaging characteristics had no statistically significances.No.3:The clinical feature of the14patients (12males and2females, with an average age of (56.4±12.6) years) included fever, right-upper-quadrant abdominal pain or discomfort, tenderness in the right-upper-quadrant abdomen. There were6patients who were accompanied with hepatitis B. The number of patients with either AFP or CA19-9was4, respectively. Patients whose lesions located in the right hepatic lobe, left and the whole liver were eight, one and five respectively. The average diameter was (8.9±3.3) cm, with less clear boundaries.2patients had edge enhancement on CT, and7had internal irregular enhancement.11patients were given anti-infection treatment, which was not effective.10patients (6died when followed up) underwent lesion resection, while4cases (all died) underwent biopsies.ConclusionsPARTⅠ1. Serum AFP and tumor thrombus were independent risk factors of death for the patients with HCC after surgery;2. CD4+T cells, CD8+T cell subsets may be associated with anti-tumor immune. The increase of CD8+CD28+T cells might enhance anti-tumor immune;3. There were so many complicated factors affecting lymphocyte subsets. Tumor was only one of these factors. The results might be more meaningful if CD4+T cells and CD8+T cells could be divided into more sub-type and dynamically observed in detail.PART Ⅱ1. Lab tests, imaging features, and patient history are helpful in differential diagnosis of IMTL from HCC/IHCC/MLC. Surgical resection is curative for IMTL.2. Older age and male gender are associated with higher possibility of biliary cystadenocarcinoma. Intra-hepatic bile duct dilation near the lesion by radiology might be instrumental. CA19-9, CEA, clinical manifestations, and other imaging features are not of value for the differential diagnosis of cystadenocarcinoma and cystadenoma.3. It is difficult to differentiate the abscess type of PLC from bacterial liver abscess before surgery or biopsy. A history of hepatitis B, increased AFP or CA19-9is helpful to identify primary liver cancer presenting as liver abscess. Preoperative anti-infective therapy should not delay surgery. It is often late to diagnose the type of PLC, with the prognosis being poor. Therefore, those patients suspected of this special type of PLC should undergo surgery as early as possible.