Question

(1) 3 General and 5 specific obectives for liver cancer.

(2) 3 General and 5 specific obectives for Schistomiasis

Answer 1

General objective of liver cancer

Loss of appetite. The patients may experience symptoms including epigastric fullness, indigestion, nausea, vomiting and diarrhea after meals. These non-specific symptoms are often neglected.

Maransis and weakness. The patients can be systemically debilitated, and cachexia can occur in a few patients with advanced disease.

Fever; and Fever is common. Patients typically develop persistent low-grade fever ranging 37.5-38 ℃. In some cases, it can be irregular/intermittent, persistent, or remittent high-grade fever. Although the high fever is clinically similar to liver abscess, it is not accompanied with chills before its onset and is refractory to antibiotic therapy. In most cases, the fever is presented as cancerous fever, which is due to the absorption of tumor necrosis products; in fewer cases, the fever can also be caused by cholangitis, which occurs due to the oppression or invasion of the tumor mass, or other infections that may easily develop after the patient’s immune system is severely weakened.

Specific objective of liver cancer

2.3.1. Blood biochemistry

Abnormal liver function including elevated aspartate aminotransferase (AST or GOT), alanine aminotransferase (ALT or GPT), serum alkaline phosphatase (AKP), lactate dehydrogenase (LDH) and bilirubin and decreased albumin can occur in PLC patients; meanwhile, immunological indicators including lymphocyte subsets can also change. Positive hepatitis B surface antigen (HBsAg), positive results of routine detection of HBV (including HBsAg, HBeAg, HBeAb and anti-HBc), and/or positive hepatitis C antibody (anti-HCV IgG, anti-HCVst, anti HCVns, and anti HCV IgM) are key markers of hepatitis virus infection, whereas HBV DNA and HCV mRNA can reflect the hepatitis C viral load.

2.3.2. Tests for tumor markers

Serum AFP and lectin reactive AFP are key indicators and the most specific tumor markers for the diagnosis of PLC. They have been widely used for the screening, early diagnosis, post-operative monitoring, and follow-up of PLC. For patients with AFP ≥400 μg/L for more than one month or ≥200 μg/L for over two months and the possibility of pregnancy, embryonal carcinoma of genital gland, or active liver disease is ruled out, PLC should be highly suspected. More importantly, concurrent imaging examinations (CT/MRI) should be performed to identify PLC-specific lesions. Still, AFP can be negative in 30-40% of PLC, which include ICC, well-differentiated and poorly differentiated HCC, or HCC filled with liquefied necrotic tissues. Therefore, AFP alone is insufficient to diagnose all PLC. The positive rate of AFP is 60 to 70 percent in PLC patients, and sometimes can show even more diverse results. Therefore, routine detection and dynamic observation should be enhanced; meanwhile, the diagnosis should be confirmed by imaging examination or ultrasound-guided biopsy.

Other markers that can be used for the auxiliary diagnosis of HCC include many serum enzymes such as γ-glutamyltransferase (GGT) and its isoenzymes, α-L-fucose glycosidase (AFU), abnormal Des-gamma-carboxy prothrombin (DCP), Golgi protein 73 (GP73), 5-nucleotide phosphodiesterase (5’NPD) isozyme, aldolase isozyme A (ALD-A), and placental glutathione S-transferase (GST). Meanwhile, ferritin (FT) and acidic ferritin (AIF) can also be useful. Carcinoembryonic antigen (CEA) and carbohydrate antigen CA19-9 can also abnormally increase in some HCC patients.

2.3.3. Radiological examinations

(I) Abdominal ultrasound (US) US has became the most important examination for liver disease because it is simple, intuitive, non-invasive, and inexpensive. By identifying the intrahepatic space-occupying lesion, suggesting its nature, identifying the liquid or solid lesions, locating the foci in the liver, and confirming their relationship with the key intrahepatic vessels, US is valuable for the treatment decision-making and guiding the surgical operation. Furthermore, US can also display the dissemination and infiltration of liver cancer within the liver and its neighboring tissues/organs. The real-time contrast-enhanced US (CEUS) can be used to observe the hemodynamics of the lesion and thus is helpful for qualitative diagnosis; however, it may yield false positive results in ICC patients. On the contrary, intra-operative US can directly explore the liver surface and avoid the ultrasound attenuation and the signal interference from abdominal wall and ribs, and thus can identify small intrahepatic lesions that are missed by pre-operative radiological examinations.

(II) Computed tomography (CT): CT is the most important radiological modelity for the diagnosis and differential diagnosis of HCC. It can be applied for the observation of the morphology and blood supply of tumors, for the detection, characterization, and staging of HCC, and for the follow-up examination after treatment of HCC. CT has high resolution. In particular, the multi-slice spiral CT has extremely fast scanning speed, which enables it to complete whole liver scanning within seconds, avoiding respiratory motion artifacts. CT is capable of performing multi-phase dynamic contrast-enhanced scan with the minimum scan thickness of 0.5 mm, significantly improving the detection rate of small HCC lesions and the accuracy of characterization. HCC usually is shown as hypodense space-occupying enhancement with clear or indistinct borders on unenhanced scan, occasionally with Halo signs. Large hepatic carcinomas commonly have central liquefaction/necrosis, which is suggestive of the nature of a lesion, helps to understand the existence of lesions in surrounding tissues or organs, and facilitates positioning during radiotherapy. enhanced scan can not only clearly display the number, size, shape and enhancement patterns of a lesion, but also definitely determine the relationship between the lesion and major blood vessels, the existence of lymph node enlargement in the hepatic hilum and abdomen as well as invasion of adjacent organs, which can provide a reliable basis for accurate staging in clinical practice and be helpful in identifying hepatic hemangiomas. Typical imaging manifestations of HCC include significant enhancement in the arterial phase, enhancement inferior to adjacent liver tissues in the venous phase and continuous subsidizing of the contrast agent in the delayed phase. Thus, enhanced scan is highly specific.

(III) Magnetic resonance imaging (MRI or MR): MRI has no radioactive radiation, high tissue resolution, and capability of multi-faceted and multi-sequence imaging, and therefore is better than CT or US in displaying and distinguishing structure changes within the HCC lesion, such as hemorrhagic necrosis and fatty degeneration as well as the capsule. MRI is superior to CT in identifying malignant or benign intrahepatic space-occupying carcinomas, in particular hemangiomas; meanwhile, it can display the portal vein or hepatic vein branches without enhancement; many evidences show that MRI is superior to CT in identifying small HCC. Especially, with the further development and application of the high field-strength MR equipment, the speed of MR scan has been greatly accelerated and now MRI can complete thin-layer, multi-phase dynamic enhanced scan, just as CT does, to fully demonstrate the enhancement patterns of a lesion and improve the lesion detection rate and qualitative accuracy. In addition, functional MR imaging techniques (such as diffusion-weighted imaging, perfusion-weighted imaging and spectral analysis) as well as the application of hepatocyte-specific contrast agents can all provide valuable additional information for lesion detection and characterization, which can further help to improve the detection sensitivity rate and qualitative accuracy of HCC as well as assess the efficacy of a variety of local treatments comprehensively and accurately.

The above three radiological modalities have their own features and advantages and therefore should be applied in an integrated and coordinated manner.

(IV) Elective hepatic artery digital subtraction angiography (DSA): DSA is most frequently adopted to clearly demonstrate small hepatic lesions and their blood supply in parallel with chemotherapy, lipiodol embolism and other treatments. The main manifestations of HCC on DSA include:
(i) Tumor blood vessels, found in the early arterial phase;
(ii) Tumor staining, found in the substantive phase;
(iii) Intrahepatic arterial shift, straightening and twisting, etc. visible in larger tumors;
(iv) Liver tumor’s invasion of intrahepatic arteries, manifested as the serrated, beaded or rigid status;
(v) Arteriovenous fistula; “pool-like” or “lake-like” contrast agent filling area, etc.

DSA can be applied not only in the diagnosis and differential diagnosis but also in preoperative or pre-treatment estimation of the extent of a lesion, especially of intrahepatic spread of sub-nodules. DSA can also provide correct and objective information including the vascular anatomic variations and the anatomical relations of major blood vessels as well as portal vein infiltration, which is of great value for judging the possibility of surgical resection and its thoroughness and determining appropriate treatment options. DSA is an invasive and traumatic technique that can be used for patients not yet confirmed after undergoing other tests. In addition, pre-surgical DSA has been proposed for resectable HCC, even those with limited imaging performance; by doing so, DSA may detect lesions non-detectable by other imaging tools and identify any potential vascular invasion.

(V) Positron emission tomography-computed tomography (PET-CT): PET-CT is a functional molecular imaging system integrating PET and CT, which can not only reflect the biochemical metabolic information of space occupation in liver through functional PET imaging, but also provide precise anatomical positioning of a lesion by CT morphological imaging. Meanwhile, whole body scan can understand the general conditions and assess the metastasis, so as to achieve the early detection of lesions and the understanding of the size and metabolic changes before and after tumor treatment. However, the sensitivity and specificity of PET-CT for clinical diagnosis of HCC still needs to be further improved. Since it has not yet universally applied in most hospitals in China, it is not recommended as a routine examination in diagnosis of HCC. Rather, it can serve as an alternative tool for other radiological examinations.

(VI) Single photon emission computed tomography (ECT): ECT whole-body bone imaging can contribute to the diagnosis of bone metastasis of HCC. Compared with X-ray and CT, it can detect bone metastasis 3-6 months earlier.

2.3.4. Needle biopsy of liver

Ultrasound-guided percutaneous liver puncture core needle biopsy (Core biopsy) or fine needle aspiration (FNA) for histological or cytological examination can obtain the pathological diagnostic evidence of HCC and determine the molecular markers, and therefore is especially useful for the definitive diagnosis, pathological classification, disease assessment, treatment decision-making, and prognosis. It has been increasingly adopted in recent years. However, there are still certain limitations or risks. Liver bleeding or needle tract implantation of HCC should be avoided during needle biopsy of liver. It should not be performed in patients with severe heart, lung, brain or kidney disorders and/or systemic failure and those with an obvious tendency of bleeding.

General objective in schistomiasis

Dermatitis

Fever

Pain in abdomen region

Specific objective in schistomiasis

Identification of eggs in stools

Diagnosis of infection is confirmed by the identification of eggs in stools. Eggs of S. mansoni are about 140 by 60 µm in size and have a lateral spine. The diagnosis is improved through the use of the Kato technique, a semiquantitative stool examination technique. Other methods that can be used are enzyme-linked immunosorbent assay, circumoval precipitation test, and alkaline phosphatase immunoassay.

Antibody detection

Antibody detection can be useful to indicate schistosome infection in people who have traveled to areas where schistosomiasis is common and in whom eggs cannot be demonstrated in fecal or urine specimens. Test sensitivity and specificity vary widely among the many tests reported for the serologic diagnosis of schistosomiasis and are dependent on both the type of antigen preparations used (crude, purified, adult worm, egg, cercarial) and the test procedure

Molecular diagnostics

Polymerase chain reaction (PCR) based testing is accurate and rapid. However, it is not frequently used in countries where the disease is common due to the cost of the equipment and the technical expertise required to run the tests. Using a microscope to detect eggs costs about US$0.40 per test whereas PCR is about $US 7 per test as of 2019. Loop-mediated isothermal amplification are being studied as they are lower cost

Ultrasonography

Ultrasonography is a major imaging tool in the diagnosis of schistosomiasis . Its ability to provide direct information about lesions in target organs, their pattern and regression after treatment makes it a valuable imaging modality

CT scan

CT findings in patients with chronic schistosomiasis includes target organ damage and peculiar calcification pattern of eggs in the lesions

MR scan

Magnetic Resonance (MR) scan has capability of demonstrating ectopic schistosomiasis such as spinal and cerebral schistosomiasis. MR scan can easily depict the hepatosplenic alterations in schistosomiasis such as heterogeneity of hepatic parenchyma, presence of peripheral perihepatic vessels, periportal fibrosis, splenomegaly, siderotic nodules and presence of dilated venous collateral vessels