Hepatic hemangioma
Hepatic hemangioma is a relatively common benign tumor of the liver, clinically spongy hemangioma is the most common, the detection rate of natural population autopsy is 0.35-7.3%, accounting for 5-20% of benign liver tumors; in recent years, with the improvement of people’s awareness of health checkups and various imaging diagnostic techniques, the detection rate of asymptomatic small hemangiomas has increased significantly. Most cases are clinically asymptomatic or mildly symptomatic, with long course and slow growth, and good prognosis.
Disease Profile
Hepatic hemangioma is a relatively common benign tumor of the liver, and cavernous hemangioma is the most common clinically, with a detection rate of 0.35-7.3% in the natural population at autopsy, accounting for 5-20% of benign liver tumors. In recent years, with the increased awareness of health checkups and advances in various diagnostic imaging techniques, the detection rate of asymptomatic small hemangiomas has increased significantly. Most cases are clinically asymptomatic or mildly symptomatic, with a long course, slow growth and good prognosis.
At present, there are not many basic and clinical studies on this disease, and there is a lack of mature and strict diagnostic and treatment criteria, and there are many ambiguous and even misconceptions about the definition of treatment options and indications. The treatment plan has not yet formed a more unified clinical pathway for doctors and patients to choose.
Causes
The exact cause of hepatic hemangioma is still unclear, but there are several theories.
(1) congenital abnormal development theory: most scholars believe that the occurrence of hemangioma is caused by congenital malformation of the terminal blood vessels of the liver, and it is generally believed that hepatic hemangioma is formed during embryonic development due to abnormal development of hepatic blood vessels and abnormal proliferation of vascular endothelial cells.
(2) Hormonal stimulation theory: some scholars have observed that the growth of hemangioma can be accelerated during female puberty, pregnancy and oral contraceptives, etc., and believe that female hormones may also be one of the pathogenic mechanisms of hemangioma.
(3) Others: such as deformation of capillary tissue after infection, resulting in capillary dilation, vascular dilation forming a vacuole after local necrosis of liver tissue, and congestion and dilation of its surrounding vessels; regional blood circulation stagnation in the liver, resulting in vascular formation of sponge-like dilation.
Disease Classification
Hepatic hemangioma can be pathologically classified into 4 types according to the amount of fibrous tissue.
(1) cavernous hemangioma, which is the most common type.
(2) Sclerosing hemangioma.
(3) hemangioendothelial cell tumors.
(4) capillary hemangioma, which is rare. At present, most of them are classified by diameter: <5cm (small hemangioma); 5-10cm (hemangioma); 10cm-15cm (giant hemangioma); >15cm (very large hemangioma), which may have some significance in guiding the treatment plan of patients with hepatic hemangioma and providing effective reference for the diagnosis and treatment of hepatic hemangioma.
Disease hazards
Hepatic hemangioma can develop at any age, and it is more common in 30-50 years old, and the literature reports more women than men, with a male to female ratio of about 1:3-6.
However, our analysis of 53859 cases of healthy population physical examination data showed that the incidence of hepatic hemangioma was 3.11%, and the incidence rates of males and females were comparable (3.36% vs. 2.88%, P>0.05), a phenomenon different from the results reported in the literature, probably due to the fact that previous literature reports analyzed outpatient or inpatient exposure cases rather than large population censuses, and most small hemangiomas were not This is probably related to the fact that most small hemangiomas were not included in the statistics.
When analyzing in depth the size composition of our census cases in males and females, we can see that the proportion of hepatic hemangiomas >5 cm in all cases was 2.56 times higher in females than in males (2.90% vs. 1.26%, P>0.05), a result that supports our hypothesis.
Further analysis of the age-incidence relationship showed an increase in incidence with increasing age, with a peak at 40-60 years of age and a subsequent decrease. This phenomenon may be explained by the fact that as age increases, the incidence of occult hemangiomas, which are initially difficult to detect, increases as they grow and are detected; after 40-60 years of age, some of the hemangiomas stop growing and some of them even recede, resulting in a decrease in incidence.
This phenomenon was verified in our analysis of 131 cases followed for more than 5 years, where the proportion of cases with enlarged hemangiomas decreased significantly with age, and the extent of the increase in the maximum diameter of hemangiomas also decreased significantly. In the analysis of the relationship between sex, age and hemangioma size, we found that female hemangiomas were larger than male hemangiomas in all age groups, and the size of hemangiomas increased significantly with age, reaching a peak at the age of 40-60 years, and then slightly decreased thereafter.
From the above data, we can easily conclude that the development of hemangioma may be influenced by changes in hormone levels, and the influence of estrogen may be more obvious, which may also explain why the incidence of hepatic hemangioma >5 cm in diameter is much higher in women than in men.
Disease symptoms
Most hepatic hemangiomas have no obvious discomfort and are usually detected during routine ultrasound examinations or abdominal surgery. When hemangiomas increase in size to more than 5 cm, non-specific abdominal symptoms may occur, including.
(1) abdominal mass: the mass is cystic in nature, without pressure pain, with smooth or non-smooth surface, and a conduction vascular murmur can sometimes be heard on auscultation at the mass.
(2) Gastrointestinal symptoms: vague pain and discomfort in the right upper abdomen, as well as loss of appetite, nausea, vomiting, belching, post-feeding distention and saturated indigestion may occur.
(3) Compression symptoms: Huge hemangioma may push and compress the surrounding tissues and organs. Compression of the lower esophagus may cause dysphagia; compression of the extrahepatic bile duct may cause obstructive jaundice and gallbladder effusion; compression of the portal venous system may cause splenomegaly and ascites; compression of the lungs may cause dyspnea and pulmonary atelectasis; compression of the stomach and duodenum may cause gastrointestinal symptoms; etc.
(4) Rupture and bleeding of hepatic hemangioma, which may present with severe pain in the upper abdomen, as well as bleeding and shock symptoms, is one of the most serious complications, mostly for larger hepatic hemangiomas growing below the costal arch that rupture and bleed due to external force, which is extremely rare
(5) Kasabach-Merritt syndrome, which is a coagulation abnormality caused by hemangioma with concomitant thrombocytopenia and massive coagulation factor depletion. The pathogenesis of Kasabach-Merritt syndrome is the retention of blood in a giant hemangioma, which causes massive depletion of red blood cells, platelets, coagulation factors II, V, VI, and fibrinogen, resulting in abnormal coagulation mechanisms, which can further develop into DIC;
(6) Others: When a hemangioma with a tip growing outside the liver is twisted, necrosis may occur, resulting in severe abdominal pain, fever and deficiency. There are also individual patients with huge hemangiomas with arteriovenous fistula formation, resulting in increased return blood volume and increased heart burden, leading to heart failure and death. There are also rare cases of biliary hemorrhage.
Ancillary tests
Imaging (e.g., ultrasound, CT, MRI) is currently the main method for diagnosing hepatic hemangioma, which lacks specific clinical manifestations. Comprehensive literature reports suggest that the diagnosis rate of hepatic hemangioma is 57.0%-90.5% for ultrasound, 94% for ultrasonography, 73.0%-92.2% for CT, 84.0-92.7% for MRI, and 62.5% for hepatic arteriography.
Ultrasound
Ultrasound examination is cheap, simple, easy to perform, with high prevalence, non-invasive and painful, safe and reliable, and can repeatedly observe lesion changes for a short period of time and obtain more information, which is inferior to CT and MRI. Ultrasound of hepatic hemangioma is mostly hyperechoic, while hypoechoic hemangioma has reticular structure, uniform density, regular shape and clear boundary. Larger hemangiomas can be lobulated in cross-section, and the internal echogenicity is still dominated by enhancement, which can be in the form of a tubular network, or irregular nodular or lumpy hypoechoic areas, and sometimes calcified hyperechoic and posterior acoustic shadowing, which is caused by thrombus formation, mechanization or calcification in the lumen of the vessel.
Contrast ultrasound
In recent years, the role of contrast ultrasound in the differential diagnosis of hepatic occlusions has been gradually recognized by a wide range of physicians. Selective use of contrast ultrasound of the liver may be considered in cases of hepatic hemangioma with atypical imaging presentation. The typical hemangioma ultrasonography shows nodular or ring-like enhancement in the periphery during the arterial phase, and then gradually expands to the center with time. This “slow-in, slow-out” enhancement feature is similar to that of spiral-enhanced CT. The sensitivity, specificity and accuracy of contrast ultrasound for small hepatic hemangiomas have been reported to be 100%, 87% and 94%.
Spiral-enhanced CT
CT scan shows well-defined round or round-like hypodense lesions in the liver parenchyma, a few of which may be irregular in shape, with a CT value of about 30HU. Dynamic CT or spiral CT multi-phase contrast-enhanced scan shows most of the specific typical performance: within 20-30s after rapid injection of contrast agent, nodular enhancement appears at the edge of the early arterial lesion, and the enhancement density is higher than that of the normal liver; with the extension of time, 50-60s after contrast agent injection;
The contrast enhancement foci fused with each other and gradually advanced to the center of the lesion, and the intensity gradually decreased; after a few minutes of delayed scanning, the whole tumor enhanced uniformly, and the enhancement density also continued to decrease, which could be higher than or equal to the enhancement density of the surrounding normal liver parenchyma, and the whole contrast enhancement process had the characteristic of “early out and late in”. In some cavernous hemangiomas, there may be irregular hypointense areas without enhancement in the center of the tumor on delayed scan, but the peripheral part of the tumor still shows this “early exit and late return” feature.
MRI
MRI shows low signal in T1-weighted and high signal in T2-weighted, with uniform intensity and clear margins, and contrast with the surrounding liver, which is described as the “light bulb sign”. When the characteristic signs of CT and MRI are clearly diagnosed, there is no need for other expensive or invasive tests, and liver aspiration biopsy should be avoided.
Other
Hepatic arteriography is an invasive test and is not necessary. In recent years, whole-body positron emission computed tomography (PET/CT) has become available and is valuable in ruling out metabolically active malignancies.
Differential diagnosis
The main differential diagnoses of hepatic hemangioma are
Primary or metastatic hepatocellular carcinoma
primary hepatocellular carcinoma often with a history of chronic hepatitis B and cirrhosis, abnormal liver function and elevated AFP; metastatic hepatocellular carcinoma, mostly multiple, often with a primary lesion in the digestive system
Hepatic echinococcosis
patients with a history of pastoral life, sheep and dog contact, positive intracutaneous test for liver encystment (Casoni test), and elevated eosinophil counts
Non-parasitic cysts of the liver
Isolated solitary hepatic cysts are easily distinguished from hepatic hemangiomas, and only a few polycystic livers may sometimes be confused with hepatic hemangiomas. polycystic liver more than 50% combined with polycystic kidney, lesions are multiple from the beginning, mostly all over the liver, ultrasound and CT show lesions as cystic cavities of variable size with smooth and intact borders, there may be family genetic factors
Others
Hepatic adenoma and hepatic hemangioendothelial cell sarcoma are rare. The former develops slowly, but the mass is hard and rubber-like; the latter develops more rapidly, has malignant tumor characteristics, and is mostly seen in adolescents.
Surgical treatment
There are controversial treatment methods for hepatic hemangioma, mainly including hemangioma resection, hemangioma suture, hepatic artery ligation, microwave curing, radiofrequency treatment, hepatic artery embolization, etc. For diffuse hepatic hemangiomas or huge hemangiomas that cannot be resected, such as hepatic dysfunction or combined with Kasabach-Merritt syndrome, liver transplantation is also feasible. For hepatic hemangiomas that require treatment, a variety of factors should be considered, and different treatment modalities should be selected based on the principle of patient benefit, safety, and effectiveness, weighing multiple factors according to the skill level and experience of the physician.
The following is a description of the different treatment modalities.
Hepatic hemangioma resection Surgical resection is reliable and safe, and complete resection is the only method that can cure it. With the development of surgical techniques, the incidence of complications and death rates associated with surgery are now very low. Nevertheless, the indications for surgery still need to be strictly controlled. Common surgical procedures include hepatic segmental resection, hemangioma debulking, laparoscopic hepatectomy, hemangioma suturing, and liver transplantation.
Hepatic segmental resection
With the development of surgical techniques and the improvement of surgical skills in liver surgery, the mortality and complications of hepatectomy have been greatly reduced, and the application has been expanded to benign lesions of the liver, among which hepatic hemangioma is the benign lesion of the liver for which hepatectomy is most frequently applied. Most patients with hepatic hemangioma do not have a history of cirrhosis, have good hepatic compensatory function, and can tolerate a wide range of hepatic resections. For huge hepatic hemangioma or multiple hemangiomas, regular hepatic segmental or lobectomy, or even hemihepatectomy is usually feasible, but the amount of hepatic resection should not exceed 70%-75% of the whole liver. The main problem of hepatic segmental resection for hepatic hemangioma is to control bleeding, because the hemangioma has rich blood supply and the tumor itself is easy to bleed, which makes the operation more difficult, and even sometimes improper operation can lead to uncontrollable hemorrhage, so how to control bleeding is the key to the success of the operation.
Hepatic hemangioma debulking surgery
The hepatic hemangioma is swollen and can compress the normal liver tissue, bile ducts and blood vessels to form a thin fibrous envelope, which is less vascularized.
This procedure was first reported by Alper et al. in 1988, and several large clinical studies comparing hepatectomy and hemangioma debridement found that the operative time, bleeding and blood transfusion of debridement were significantly less than those of hepatectomy; the damage to the liver was light, normal liver tissue was preserved to the maximum extent, and patients recovered quickly after surgery; the damage to important intrahepatic vessels and bile ducts was reduced, bleeding was decreased, and the incidence of biliary fistula was reduced. The incidence of biliary fistula is reduced.
It has become the main procedure for the treatment of hepatic hemangioma, and is now advocated by many scholars at home and abroad. The rule of thumb hepatectomy is only used when malignancy is suspected, or when a lobe of the liver is completely occupied by a tumor. However, some scholars believe that in some cases, it is difficult to confirm the gap between the hemangioma and the liver parenchyma during surgery, and peeling may cause more bleeding, especially for hemangiomas close to the hepatic vein trunk, posterior inferior vena cava and other important structures, blunt peeling may easily tear large vessels or damage the tumor, leading to uncontrollable hemorrhage.
Expert opinion
(1) If the tumor is located in the left outer lobe of the liver, hepatectomy should be chosen because it is easier to operate. In addition, hepatectomy is also performed when multiple hemangiomas are confined to a particular lobe of the liver, in which case removing the tumors one by one would be very damaging, bleeding and time-consuming.
(2) Right lobe hemangioma debulking has advantages over hepatectomy due to the relatively complex and traumatic technique of right hepatectomy.
(3) Hemangioma in the middle lobe of the liver is close to the hepatic hilum and not only has a close relationship with the large blood vessels entering and leaving the liver, but also may invade the left and right hepatic lobes, so hepatectomy is more difficult for such tumors.
(4) Hepatectomy is appropriate for hemangioma of huge size. Because huge hemangioma occupies the left or right lobe or a segment of the liver, compressing the liver tissue and leaving little normal liver tissue in the liver lobe or segment where the lesion is located, regular hepatic lobectomy or hepatic segment resection does not lose much normal liver tissue and avoids hemorrhage from the tumor envelope or large blood vessel tear that may result from the removal.
(5) For those who cannot exclude primary hepatocellular carcinoma or have history of other malignant tumors and suspect liver metastasis, regular liver resection or local resection with certain “safe margin” is appropriate.
(6) For multiple hemangiomas distributed in different lobes or segments of the liver, a combination of both surgical approaches can be used.
Laparoscopic hepatectomy
The laparoscopic hepatectomy technique has become increasingly mature, and its minimally invasive advantages such as less trauma, fewer complications and faster recovery are very obvious, and its application rate is increasing year by year. Its postoperative complications are similar to those of open surgery, and the postoperative recovery is fast and the hospital stay is short. Laparoscopic left outer lobe and left hemihepatectomy is expected to become the standard procedure for the treatment of hepatic hemangioma.
However, hepatic hemangiomas in the right posterior lobe, middle liver lobe and caudate lobe are difficult to perform total laparoscopic hepatectomy because of their special location and susceptibility to hemorrhage. Although the scope of laparoscopic hepatectomy for hepatic hemangioma is currently limited, with the development and breakthrough of laparoscopic technology, laparoscopic hepatectomy for hepatic hemangioma will have a broad application prospect.
Liver transplantation
Hepatic hemangioma is a benign lesion, and liver transplantation is only used for unresectable giant hepatic hemangioma and the occurrence of serious complications such as Kasabach-Merritt syndrome, which is not yet widely performed.
Suture ligation
Hepatic hemangioma suture ligation is used to treat hemangioma by suturing the hemangioma to make it shrink, mechanize, or even disappear. Due to the lack of understanding of liver anatomy in the past, the smaller the tumor body is, the longer the embrace ligation time is, the better the effect is, while the larger the tumor body is, the shorter the ligation time is, the worse the effect is. The postoperative recurrence rate of hemangioma stapling alone is very high and is no longer recommended for routine use. Hepatic artery
Ligation
Hepatic hemangiomas are usually supplied by the hepatic artery, and ligation of the hepatic artery can temporarily reduce the size of the tumor and soften it. Combined with postoperative radiotherapy, it can harden the tumor mechanically, which is useful for improving symptoms and controlling tumor growth. However, due to the presence of collateral circulation, the efficacy is mostly difficult to maintain and the long-term effect is limited. Hepatic artery ligation is mainly used for unresectable giant hemangiomas. Due to the adoption of new technologies in recent years, hemangiomas previously thought to be unresectable can now be safely resected in technically superior hepatobiliary surgery centers, so simple hepatic artery ligation is rarely used to treat hepatic hemangiomas.
Complications
1. Postoperative intra-abdominal hemorrhage
It is a common and serious postoperative complication, which needs extra attention. Most patients with hepatic hemangioma do not have cirrhosis and have good preoperative liver function, so postoperative bleeding due to coagulation dysfunction is rare. For postoperative hemangioma bleeding, active dissection should be performed, suspicious bleeding points should be tightly sutured with vascular sutures, and the bleeding situation should be closely monitored after surgery.
2.Postoperative bile leak
The failure to detect and suture a certain tiny bile duct during surgery is the main reason for postoperative bile leakage after hepatic hemangioma debridement with large trauma. Bile leakage after hepatic hemangioma surgery needs to keep the drainage unobstructed, usually it can heal by itself, but if necessary, it needs to be drained by percutaneous puncture.
3.Postoperative liver insufficiency or failure
It is often associated with failure to adequately assess the volume of the residual liver before surgery, other underlying diseases of the liver, intraoperative hemorrhage, prolonged hypotensive shock, intraoperative injury to the incoming or outgoing hepatic vessels preserving the liver lobe, postoperative thrombosis of the portal vein trunk, and torsion of the residual liver affecting hepatic blood flow. Most patients with hepatic hemangioma have elevated transaminases after surgery, which peak 2-3 days after surgery and generally fall to the normal range in about 1 week, and some patients may also have mildly increased bilirubin, which gradually improves with liver support therapy. In case of irreversible liver failure, the only option is to perform an emergency liver transplant.
Non-surgical treatment
Hepatic artery embolization (TAE)
TAE for hepatic hemangioma is based on the experience of TAE for hepatocellular carcinoma. The theory is based on the fact that hepatic hemangioma is mainly supplied by hepatic artery, and thrombus can be formed in the tumor after embolization of artery, and the thrombus can be mechanized and fibrotic to form fibromatous structure in the tumor to shrink and harden the hemangioma. However, it is still controversial to treat hepatic hemangioma with TAE because of the poor long-term effect of large hemangioma and the difficulty of shrinking and mechanizing the tumor.
Moreover, while embolizing the hemangioma during embolization, the embolization agent often involves the normal blood supply of the porta hepatis and intrahepatic bile ducts, which can cause some serious complications, such as biliary tumor, hepatocellular necrosis, liver abscess, biliary cirrhosis, biliary ischemic stenosis and biliary arteriovenous fistula. Meanwhile, although the side effects of vascular sclerosing agent Pingyangmycin are few, the side effects of causing pulmonary fibrosis and damaging the arterial intima when used intra-arterially in high doses should not be underestimated.
Microwave curettage and radiofrequency treatment of hepatic hemangioma
Microwave curing and radiofrequency treatment of hepatic hemangioma can be converted into heat energy and cause the surrounding tissues to coagulate, causing local atrophy and hardening of the tumor to achieve the purpose of curing the tumor. With this method, the first hepatic portal must be blocked to reduce blood flow within the tumor. For larger hepatic hemangiomas, microwave treatment is difficult to completely cure the tumor and has a high recurrence rate after surgery. The principle of radiofrequency is similar to microwave, and it is effective in treating small hemangiomas, but it is not effective in treating >8cm, and it may even cause hemorrhage.
In particular, the tumor wall tissue is thin and the tumor with little fibrous tissue is prone to uncontrollable bleeding during puncture, which is a contraindication to microwave curing or radiofrequency treatment. Meanwhile, microwave curing and radiofrequency ablation of hepatic hemangioma can cause the destruction of a large number of red blood cells and release a large amount of hemoglobin, which can cause acute renal failure and hemoglobinuria. Therefore, microwave curing or radiofrequency treatment of hemangioma under ultrasound guidance should be done with great caution. If the tumor is located in the center of the liver, near the large blood vessels, near the gallbladder and gastrointestinal organs, and near the diaphragm, it may cause serious complications due to damage to the adjacent organs, and is not suitable for radiofrequency ablation treatment.
Expert opinion
With a better understanding of the natural course of hepatic hemangioma, there is a new and different understanding of the appropriate timing and indications for surgery. The focus of hemangioma treatment is on symptomatic relief and prophylactic control of complications and rupture and bleeding associated with large, multiple hemangiomas, with due consideration of the possible complications associated with different treatment options, and not over-treating controversial patients, especially those without clinical signs and symptoms, with unnecessary complications.
The current indications for the treatment of hepatic hemangioma are confusing, ranging from the size of the hepatic hemangioma in terms of diameter, which should be treated surgically if it is >4-5 cm, to the symptoms and complications. From our data, the symptoms of most hemangiomas are non-specific and difficult to distinguish from gastrointestinal and biliary tract symptoms, and rarely cause symptoms when the hemangioma is less than 5 cm in diameter. Therefore, our surgical indications are currently considered as follows
(1) right liver > 8 cm, left liver and caudate lobe > 6 cm with definite symptoms or exophytic or growth rate > 1-2 cm/year
(2) Hemangioma > 10 cm in diameter;
(3) with complications, such as infected fever, bleeding and with significant hematological abnormalities
(4) For patients older than 60 years of age, the indications should be more stringent because the hemangioma may no longer grow or grow more slowly.
(5) In view of the fact that hepatic hemangioma may increase faster during pregnancy and may cause rupture and hemorrhage during childbirth, the giant hepatic hemangioma in young women should be actively removed surgically.
(6) For those who are engaged in strenuous sports, such as boxers and soccer players, surgical resection can be considered.
(7) If the growth rate of the tumor is fast and other lesions cannot be excluded during the follow-up. Clear clinical symptoms, exophytic nature, rapid growth rate and concomitant hematologic abnormalities should be the indications for surgery in such patients.
Among the treatment options for hepatic hemangioma, hemangioma debulking is significantly superior to resection in terms of safety, thoroughness, bleeding, blood transfusion, and length of hospital stay. In some hemangiomas located in the margin, exophytic, and left hepatic outer lobe, laparoscopic resection can be applied to achieve less trauma and faster recovery. tae has certain efficacy and minimally invasive advantages in the treatment of small hemangiomas, but hemangiomas <5 cm often do not need to be treated, while tae treatment of large hemangiomas has poor long-term results, and serious complications may occur as well as increase the difficulty during surgical treatment.
The purely tendentious medical practice of mobilizing patients for treatment without indications for surgery when hepatic hemangiomas are found on physical examination is strongly opposed. Interventional treatment can be applied in selective and special cases, such as advanced age, contraindication to surgery for systemic complications, inoperability of giant hemangiomas, and strong requests from patients.
In conclusion, the diagnosis and treatment of hepatic hemangioma is progressing, and as a common and frequent disease of the liver, clinical attention should be paid to it, and treatment should be cautious and strict, with attention to differentiation from other lesions of the liver, especially malignant diseases.