Resection of giant liver adenoma in a 17-year-old adolescent boy using venovenous bypass, total hepatic vascular isolation, and in situ cooling

Giant liver adenomas are rare pediatric tumors. Hepatocellular adenomas account for approximately 2% to 4% of all pediatric liver tumors. We present the case of a biopsy-proven 21 × 20.5 × 10.5-cm hepatocellular adenoma in a 17-year-old adolescent boy resected using venovenous bypass and total hepatic isolation. Hepatic adenomas of this size are historically treated with orthotopic liver transplantation. Resection of a massive centrally located giant liver adenoma using total hepatic vascular isolation and venovenous bypass with in situ hepatic cooling and is not previously reported. By combining these techniques, we were able to defer the risks of orthotopic liver transplantation and life-long immunosuppression for our patient. The patient's recovery was uncomplicated and hepatic regeneration was excellent. At 9 months' follow-up, the patient reported enjoying an athletic adolescent life-style with no evidence of recurrence.     

肝硬化门脉高压症治疗的新途径——干细胞移植研究进展

肝干细胞是多源性的,可分为肝源性肝干细胞和非肝源性肝干细胞两大类。多种成体组织来源的干细胞可在受者(包括鼠和人)肝脏内分化为肝细胞和胆管上皮细胞,为成体干细胞移植治疗肝硬化门脉高压提供了新思路。在临床应用中,肝干细胞移植具有移植技术简单、价格相对低廉,免疫源性小、易于低温保存,具有广泛的扩展性,体外基因转染率高,并能稳定高效地表达外源基因等优点;但肝内干细胞移植是否会引起肝脏肿瘤等问题尚未明确。     

Kupffer cells in hepatocellular adenomas

Hepatocellular adenomas are usually visualized as defects on technetium-99m-sulfur colloid liver scans, a fact which has been attributed to the absence of phagocytic Kupffer cells in the tumors. To determine whether this is true, seven hepatocellular adenomas were subjected to immunoperoxidase staining for lysozyme, a marker of mononuclear phagocytes. The Kupffer cells were counted in the tumors and surrounding non-neoplastic liver. All hepatocellular adenomas studied were found to contain Kupffer cells. Three tumors had fewer Kupffer cells than the surrounding liver. Three had about the same number as the surrounding liver, and one had more Kupffer cells than the non-neoplastic liver. Thus, the lack of phagocytosis of colloid in liver scans is probably due to something other than a deficiency of Kupffer cells in the hepatocellular adenomas.     

A new case of hepatic adenomatosis treated with orthotopic liver transplantation]

Hepatic adenomatosis is a rare disease with multiple hepatic adenomas (10 or more), not associated with an history of oral contraceptive use or anabolic steroids use or with glycogen storage disease. A new case is reported in a 23 year-old woman who consulted for an abdominal mass and who had more than 50 adenomas of the liver. The suspicion of malignant transformation by the elevation of the alpha-foetoprotein, and the diffuse affectation of the liver, with minimum free parenchyma, suggested to carry out an orthotopic liver transplantation. The definitive histological examination of the surgical specimen confirmed the existence of local areas of hepatocellular carcinoma.     

c-kit在人肝硬化及肝细胞肝癌组织中的表达及意义

目的探讨肝脏祖细胞标志物c-kit在人肝硬化及肝细胞肝癌（HCC）组织中的表达及其与临床病理特征的关系。方法对30例肝硬化、40例肝细胞肝癌标本及3例正常组织标本进行常规组织学观察以及c-kit、CD45免疫组化染色,对肿瘤细胞的分化程度及肝硬化组织门静脉炎症程度进行分型和评分,分析c-kit表达与肝硬化及肝细胞肝癌的临床病理特征的联系。结果正常肝脏中c-kit染色阴性。20／30例肝硬化中发现c-kit（＋）细胞,位于门脉周围区域和纤维间隔内,个别阳性细胞整合到成熟胆管,肝硬化结节中没有发现c-kit（＋）细胞。19／40例HCC组织中存在c-kit （＋）肿瘤细胞,在肿瘤细胞之间或肿瘤结节周围分散分布。HBsAg及Anti-HBc在c-kit（＋）与c-kit （-）HCC之间表达有显著性差异（χ^2=5．063,P〈0．05;χ^2=6．667,P〈0．05）。c-kit表达与肿瘤的分化程度紧密相关（χ^2=10．384,P〈0．05）,分化程度越低,c-kit表达越高。结论骨髓来源的肝脏祖细胞参与了部分肝硬化病变过程中的肝再生及HCC的形成和发展,c-kit表达情况对于判断HCC预后有一定意义。     

The frequency and histology of hepatic tissue in germ cell tumors

The frequency of hepatic tissue and its histological characteristics were examined in 516 germ cell tumors. Hepatic tissue was observed in 48 cases (9.3%). The incidence of hepatic tissue was low in tumors of the ovary (5%), high in both retroperitoneal (27%) and sacro-coccygeal (24%) tumors, and low in both mature (0.3%) and immature teratomas (11%). It was usually encountered in infancy, and the frequency was high in both yolk sac tumors (48%) and mixed germ cell tumors (52%). The hepatic tissue found mainly in mature or immature grade 1 teratomas was similar to adult normal human liver tissue (Ha-type). Tissue in areas consisting of some immature somatic elements of a mixed germ cell tumor was similar to embryonic or fetal liver tissue (Hf-type). Many hepatic nests found in a polyembryoma were of both Ha- and Hf-types. The hepatic tissue found in close relation to yolk sac elements showed predominantly hepatocellular carcinoma-like features (HCLS). Immunohistochemically, the cytoplasm of adult liver-type cells was positive for alpha-1-antitrypsin (AAT), human albumin (ALB), and the third (C3) and fourth (C4) components of the complement system. The cytoplasm of fetal liver-type cells showed the same positivity; in addition, these cells were positive for alpha-fetoprotein (AFP) in 25% of the cases. The cytoplasm of hepatic cells of HCLS was positive for AFP, AAT, ALB, C3, and C4. A weakly positive reaction for CEA and CA19-9 was observed in bile duct-like structure in some Hf-type cases.     

Management issues regarding hepatic adenomatosis.

Hepatic adenomatosis is a rare disease defined by multiple hepatic adenomas. There is controversy with regard to the optimal treatment for this disease because the potential for intraperitoneal hemorrhage or malignant transformation of the tumors is difficult to estimate. Furthermore, the technical difficulties of complete resection of all adenomas present unique operative challenges. We report experience with two patients and reviewed all reported cases from 1977. We define hepatic adenomatosis as five or more hepatic adenomas not associated with a medical history of glycogen storage disease, anabolic steroid use, or oral contraceptive use. The incidence of hepatic adenomatosis was preponderate among women [20 of 32 patients (63%)]. Thirteen of 32 patients (41%) had intratumoral bleeding, including four patients with intraperitoneal hemorrhage. Ten of 13 patients (77%) with intratumoral bleeding complained of abdominal pain; overall, 19 of 32 patients (59%) had abdominal pain. Twelve patients underwent hepatic resection, 6 patients underwent liver transplantation with no reported mortality, and 14 patients had no surgical treatment. Hepatocellular carcinoma was histologically confirmed in 2 of 32 patients (6%). Larger symptomatic adenomas exposed to liver surface have a bleeding propensity and should be surgically resected. Routine biopsy of other small nodules suspected as adenomas is recommended for definitive diagnosis.     

A clinicopathologic study of steroid-related liver tumors.

A registry of liver tumors was started in late 1973 in an attempt to assess the relationship of these tumors to oral contraceptives or to other environmental factors. This report is concerned with the pathological aspects and the possible pathogenesis of the first 101 tumors accessioned. There were 44 instances of focal nodular hyperplasia, 40 adenomas, four unclassified but probably benign tumors, and 13 hepatocellular carcinomas. Eighty-one patients took oral contraceptives; six were associated with pregnancy; three had taken estrogens for long periods of time; one had a thecoma; four never took sex steroids; and in five the history was unknown. Tumor rupture and intrahepatic hemorrhage were frequent complications. It is possible that the vascular lesions associated with focal nodular hyperplasia could play a part in their pathogenesis as well as with rupture. Foci of adenomatous hyperplasia may be related to the development of adenomas. The association of these tumors with sex steroids could be coincidental. The fact that none of the patients had cirrhosis of liver fibrosis, and that androgenic anabolic steroid therapy has been associated with hepatocellular carcinomas in males, suggests that further study of the problem is necessary.     

Reticulin loss in benign fatty liver: an important diagnostic pitfall when considering a diagnosis of hepatocellular carcinoma

Reticulin stains are commonly used in surgical pathology to assess mass lesions for the possibility of hepatocellular carcinoma. The loss of normal reticulin staining can help support a diagnosis of hepatocellular carcinoma, and this stain has proven to be particularly helpful on limited biopsies and fine-needle aspirates. However, an underappreciated diagnostic pitfall is that non-neoplastic liver tissue can also show reticulin loss when there is fatty change. To further characterize this important diagnostic pitfall, reticulin staining was studied in cases of nonalcoholic steatosis, nonalcoholic steatohepatitis, and hepatic adenomas with fatty change. A total of 112 cases with varying degrees of steatosis were collected from 4 academic centers, including 49 cases of steatosis, 49 cases of steatohepatitis, and 14 hepatic adenomas with fatty change. Steatosis was graded as mild (5% to 30% macrovesicular steatosis), moderate (31% to 60%), and marked (>60%). Reticulin stains were scored as the number of foci with diminished reticulin staining in 10 hpf. A focus of diminished reticulin was scored when the extent of reticulin loss was similar to that seen in hepatocellular carcinomas. In the total study set, 28 cases showed mild steatosis, 40 cases showed moderate steatosis, and 44 cases showed marked steatosis. Interestingly, increasing amounts of fat were associated with decreased reticulin staining. For mild steatosis, reticulin loss was rare, with the number of foci of reticulin loss per 10 hpf averaging 0.8 (range, 0 to 3); however, this increased for moderate steatosis, which showed a mean of 3.0 foci per 10 hpf (range, 0 to 5), and was most prominent with marked steatosis, which showed an average of 5.8 foci of reticulin loss per 10 hpf (range, 5 to 8). An almost identical pattern was seen in cases of nonalcoholic steatohepatitis. Overall, reticulin loss was not associated with the degree of inflammation or with the presence or absence of balloon cell change. Reticulin loss also did not correlate with fibrosis stage. In hepatic adenomas, reticulin loss was seen only in areas of fatty change, and decreased reticulin again paralleled the amount of steatosis, with more prominent reticulin loss in those cases with marked steatosis. In conclusion, reticulin loss that reaches levels seen in hepatocellular carcinoma can be seen focally in benign liver tissues with fatty change. Overall, loss of reticulin is more common and more extensive with marked fatty change and does not seem to be linked to inflammation or fibrosis stage. Loss of reticulin can also be seen in hepatic adenomas with fatty change. Increased awareness of this important diagnostic pitfall will help prevent overcalling of reticulin loss when evaluating biopsies and resections of hepatic neoplasms with fatty change.     

Atypical bile duct adenoma, clear cell type: a previously undescribed tumor of the liver.

A variable proportion of bile duct adenomas of the liver are still confused with metastatic well-differentiated adenocarcinoma by surgeons and pathologists. We present here three examples of previously undescribed primary hepatic bile duct tumors that were composed almost entirely of clear cells that closely mimicked metastatic renal cell carcinoma. They were interpreted as atypical bile duct adenomas and occurred in two males and one female whose ages ranged from 25 to 64 years. All three tumors were incidental findings and measured from 0.8 to 1.1 cm. The clear neoplastic cells showed mild nuclear atypia and no mitotic activity. They were arranged in tubules and nests that focally infiltrated the hepatic parenchyma. For comparison, a case of clear cell cholangiocarcinoma and 13 conventional bile duct adenomas were examined. The clear cell cholangiocarcinoma was larger (6.0 cm) and had the tubular pattern of conventional cholangiocarcinoma and an abundant desmoplastic stroma. The clear cells of this tumor exhibited greater nuclear atypia and increased mitotic activity. All three atypical bile duct adenomas expressed cytokeratin (CK) 7, p53 protein, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA); they were negative for CK20, vimentin, Hep Par 1, chromogranin, and prostatic specific antigen (PSA) and exhibited less than 10% of Ki-67-positive nuclei. One atypical bile duct adenoma displayed luminal immunoreactivity for villin. With the exception of Ki-67 reactivity, the 13 conventional bile duct adenomas and the clear cell cholangiocarcinoma had essentially a similar immunohistochemical profile as that of the atypical clear cell bile duct adenomas. The absence of an extrahepatic primary tumor, the histologic features, the immunohistochemical profile, and the fact that all patients are symptom-free 2 months to 18 years after wedge liver biopsy support the interpretation of atypical clear cell bile duct adenoma. The differential diagnosis with clear cell hepatocellular carcinoma and metastatic clear cell carcinomas is discussed.     

Total vascular exclusion for hepatic resection in cirrhotic patients. Application of venovenous bypass.

Hepatic vascular exclusion with double venovenous bypass using a centrifugal force pump was used in major hepatic resections in eight patients with hepatocellular carcinoma combined with cirrhosis, and results were compared with those in four patients with hepatocellular carcinoma without cirrhosis and eight with metastatic tumors without cirrhosis among 521 patients undergoing liver resection. Concomitant resection of the retrohepatic inferior vena cava was performed in three of eight patients with cirrhosis and five of 12 patients without cirrhosis. All patients, except one with cirrhosis, tolerated major resection without any hemodynamic impairment, which is often observed in hepatic vascular exclusion without venovenous bypass. One patient, whose complete inflow occlusion period was 70 minutes, died of liver failure. In this patient, the recovery of the arterial ketone body ratio above 1.0 was delayed until 3 days after recirculation, whereas the ratio in the others recovered promptly. Postoperative complications such as increased bilirubin level, pleural effusion, and gastrointestinal tract bleeding were observed in seven of eight patients with cirrhosis compared with six of 12 without cirrhosis. Hepatic vascular exclusion is feasible even in cirrhotics as long as it is applied with venovenous bypass and is kept within the time limit of 60 minutes.     

Management of liver cell adenoma and focal nodular hyperplasia

Since 1975 six cases with hepatic adenoma (5 females, 1 male) and five cases with focal nodular hyperplasia (3 females, 2 males) have been treated at our hospital. Four of the five women with hepatic adenoma took oral contraceptive pills before the diagnosis was made, only one patient took the pills in the group with focal nodular hyperplasia. Hepatic adenomas were resected electively in three patients; one patient underwent operation because of ruptureed adenoma with intraabdominal hemorrhage. In the other two cases with hepatic adenoma resections were not possible, but both tumors have regressed after the cessation of oral contraceptives. One patient in the group with focal nodular hyperplasia underwent liver resection because of intratumoral hemorrhage with recurrent pain; in the other four cases no treatment was done as symptoms were absent. We recommend elective resection for hepatic adenoma because of the high risk of spontaneous ruptur. Embolization or ligation of the hepatic artery are alternative procedures when resection is not possible and tumors do not regress after the cessation of oral contraceptives. On the other hand a more conservative attitude is suggested for focal nodular hyperplasia because those patients do not frequently bleed; resection is indicated in case of symptoms or growth of tumor.     

Hepatic serial resection. Portal vein resection followed by hepatic resection in second time

Hepatic resection still remains the only potential curative treatment for either primary or secondary malignant liver tumors. In order to increase the resectability of initially considered non-resectable tumors and to decrease the posthepatectomy morbidity and mortality, ligature of a portal branch with consecutive hepatic resection is recommended. The ligature of a portal venous branch was performed in 12 patients with gross hepatic tumor: hepatocellular carcinoma (2), peripheral cholangiocarcinoma (5), hepatic metastases from colorectal cancer (5). Two-stage hepatectomy was performed in 5 patients. The interval between the two operations ranged between 4 weeks and 6 months. Hepatic resection could not be performed in 7 cases due to the loco-regional progression of the disease (4 cases) or to the absence of the hypertrophy-atrophy process (3 cases). Hepatic failure occurred posthepatectomy in 2 patients, resulting in the death of one of the patients. Two patients died at 5 and 10 months respectively while two other patients are still alive, free of recurrence at 6 and 12 months respectively. In conclusion, portal vein ligature can be considered in selected cases of unresectable gross hepatic tumors that can be eventually, resected in a second operation. The two-staged hepatectomy is not always feasible. Moreover, the hypertrophy of the controlateral lobe does not always prevent the postoperative hepatic failure..     

Laparoscopic Liver Resection in Patients with a History of Upper Abdominal Surgery

Background  

The liver is the organ where tumors most frequently metastasize. Hepatic recurrence after resection of hepatocellular carcinoma also occasionally occurs. With the increasing use of laparoscopic surgery for hepatic tumors, there may be a high probability that laparoscopic liver resection can be performed in patients with a surgical history. The purpose of this study was to assess the feasibility and clinical outcomes of laparoscopic liver resection in patients a history of upper abdominal surgery.     

少见类型的肝脏良性肿瘤和瘤样病变

目的：总结少见类型的肝脏良性肿瘤和瘤样病变的诊治经验。方法：对1980年1月－2000年6月，收治的并经手术和病理证实的58例原发于肝脏的少见的良性肿瘤和瘤样病变的临床资料进行回顾性分析。结果：58例中炎性假瘤26例，局灶性增生性病变8例，肝细胞腺瘤7例，脂肪类肿瘤7例，囊腺瘤5例，肝结核3例及错构瘤和神经纤维瘤各1例。男性33例，女性25例，年龄20－66岁，平均42．7岁，82．8％的病人有临床症状，17．2％的病人无任何症状，93．1％为单发病灶，6．9％为多发病灶，手术方式：病灶局部除30例，肝段切除14例，肝叶切除9例，肝活检2例，肝动脉结扎2例，囊腔引流加肝动脉结扎1例，未发生严重并发症和手术死亡。结论：近年随着影像检查技术的普及，少见类型的肝脏良性肿瘤和瘤样病变的发生率有所增加，然而影像技术在诊断上缺乏特异性，在鉴别诊断上往往存在困难，故我们应熟悉上述病变的临床情况，影像特征和处理方法。     

人肝癌裸鼠NKG2D受体的表达及对NK细胞毒活性的影响

目的 通过研究原发性肝癌中NK细胞的细胞毒活性变化及其活化性受体NKG2D的表达,观察肝脏和脾脏组织病理变化,探讨NK细胞免疫抑制机制,为原发性肝癌的免疫治疗提供理论依据。方法 ①建立人肝癌裸鼠皮下-肝原位移植瘤模型：先用人肝癌细胞株Hep3B接种于裸鼠皮下,形成皮下移植瘤,然后用此移植瘤组织再接种于裸鼠肝内,建立肝原位移植瘤模型（间接肝原位移植瘤模型）;②检测裸鼠原发性肝癌对NK细胞免疫活性的影响：分离裸鼠外周血、肝脏及脾脏组织NK细胞,LDH方法检测NK细胞的细胞毒活性,流式细胞技术检测不同组织NK细胞NKG2D表达百分率,H-E染色观察肝脏移植瘤对肝脏和脾脏淋巴细胞的影响。结果 ①外周血、肝脏及脾脏的NK细胞毒活性及NKG2D受体表达随着肿瘤生长逐渐下降,其中肝脏NK细胞毒活性及NKG2D表达下降明显;②荷瘤裸鼠肝脏癌组织与皮下瘤相同,癌组织异型性与时间呈正相关,脾脏淋巴小结在第4周增生明显,第8周小梁结构增多。结论 原发性肝癌通过下调NKG2D的表达,对NK细胞有免疫抑制作用,这种作用主要发生在肝脏,但对外周血和脾脏也有影响。     

Treatment for hepatocellular carcinoma associated with tumor embolus in the inferior vena cava

Hepatic resection and removal of the tumor embolus was performed in six patients with hepatocellular carcinoma associated with tumor embolus in the inferior vena cava, without distant metastasis. Hepatic resection was performed in five patients under total hepatic vascular exclusion (THVE) with veno-venous bypass, using a centrifugal force pump and in one patient, under simple THVE without the bypass. In one patient, partial resection of segment VIII was performed, in one, a central bi-segmentectomy, and in four, right hepatic lobectomies were performed. Surgery was safely performed in all the 5 patients under THVE using the centrifugal force pump. One patient who underwent partial hepatic resection under the simple THVE, suffered cardiac arrest during surgery, but resuscitation was successful. Three patients died of reccurence within 1 year. The other three patients survived for 10 months, 2 years and 10 months, and 3 years and 10 months, respectively, after surgery. There were recurrences in the first two, patients, in both, treated by transcatheter arterial embolization, and to date, the third patient is disease-free. Hepatic resection was safely performed in patients with hepatocellular carcinoma associated with tumor embolus in the inferior vena cava, under conditions of THVE using the centrifugal force pump. Prolonged survival can be anticipated, with favorable liver function, in those patients in whom most of the lesion is resected.     

Molecular Pathogenesis of Hepatic Adenomas and Its Implications for Surgical Management

Introduction

Hepatic adenomas (HAs) are benign tumors of the liver, which can be solitary or multiple, and have a definite risk of malignant degeneration.

Discussion

The pathogenesis and natural history of this disease entity were previously unknown. Recent research into the molecular pathogenesis of this condition has provided evidence for the malignant transformation of some of these adenomas. In the current article, we discuss the current evidence on the molecular biology underlying malignant transformation of hepatic adenomas and the implications for the surgical management of this disease.     

Major hepatic resection. A 25-year experience.

Major hepatic resections were performed on 138 patients for a variety of conditions. There was one intraoperative death. Including this patient, there were 15 deaths within 30 days of the operation (operative mortality 10.9%). Important postoperative complications were intra-abdominal sepsis (17%), biliary leak (11%), hepatic failure (8%), and hemorrhage (6%). The results of 30 resections for the benign lesions, liver cell adenoma, focal nodular hyperplasia, hemangioma, and cystadenoma showed no operative mortality and low morbidity. Of 26 patients with hepatocellular carcinoma, seven died within a month of operation. The cumulative survival of the 26 at five years was 38%, and of the 19 who survived the procedure, 51%. Poor survival followed resections for cholangiocarcinoma and "mixed tumors." The five-year cumulative survival of 22 patients who had colorectal metastases excised was 31%. Apart from a patient with carcinoid, prolonged survival was rare after resection of other secondaries and after en bloc resections for tumors directly invading the liver. Hepatic resection was of value in the management of some patients with hepatic trauma, Caroli's disease, liver cysts, and intrahepatic stones.     

A review of liver masses in pregnancy and a proposed algorithm for their diagnosis and management

BACKGROUND: Liver masses in pregnancy are rare; some behave aggressively while others remain indolent. The paucity of case series has hindered the development of a defined approach to their diagnosis and management. This paper presents an algorithm for the diagnosis and management of hepatic hemangiomas, focal nodular hyperplasia, liver cell adenomas and hepatocellular carcinoma associated with pregnancy based on our own experience and literature review. DATA SOURCES: A Medline search from 1966 to present was performed. Seven additional illustrative cases from our institution are included. Twenty pregnancies with hepatic hemangiomas, 37 with focal nodular hyperplasias, 26 with liver cell adenomas and 33 with hepatocellular carcinomas were identified. CONCLUSIONS: Gestational hepatic hemangiomas and focal nodular hyperplasia behave indolently and can be observed. Liver cell adenomas often require surgery, but small, asymptomatic lesions may be carefully observed. Meticulous observation postpartum is mandatory. As pregnancy impacts survival in hepatocellular carcinoma, resection maybe indicated.