Successful resection, using pancreas-sparing duodenectomy, of extrahepatically growing hepatocellular carcinoma associated with direct duodenal invasion

A 50‐year‐old man with extrahepatically growing hepatocellular carcinoma (HCC) associated with direct duodenal invasion underwent a right posterior segmentectomy associated with pancreas‐sparing duodenectomy. Neither periduodenal lymph‐node metastasis nor pancreatic invasion was detected, thus we separated the supra‐ampullary duodenum from the pancreatic head and performed pancreas‐sparing supra‐ampullary duodenectomy. The resected specimen was observed to be a centrally necrotic tumor that had infiltrated the duodenal wall, resulting in exposure of the lumen. Pathology examination revealed that the tumor consisted of poorly differentiated HCC, which had extensively infiltrated the mucosa of the duodenum. Gastrointestinal tract involvement in patients with HCC is rare, and pancreas‐sparing duodenectomy is a safe and effective treatment for patients with HCC associated with direct duodenal invasion.     

Hepatocellular carcinoma complicated by gastrointestinal hemorrhage caused by direct tumor invasion of stomach

A 65-year-old man with multiple hepatocellular carcinoma (HCC) underwent intra-hepato-arterial chemotherapy (IHAC) through an implantable port over a period of 10 months after transcatheter arterial embolization (TAE) had been performed three times. TAE was performed twice more, and radiotherapy (total dose, 30 Gy; given over a 3-week period) was given for progressive disease in the lateral segment of the liver. Three months after the radiotherapy had finished, the patient suddenly developed melena. Diagnostic imaging revealed gastrointestinal (GI) hemorrhage from HCC invading the stomach, and total gastrectomy and lateral segmentectomy of the liver were performed because the bleeding could not be controlled. The resected specimen disclosed a centrally necrotic tumor that had invaded the lesser gastric curvature and perforated into the lumen. Pathology examination revealed that the HCC had expansively invaded the gastric mucosa, resulting in exposure in the lumen. The possible mechanisms of direct GI invasion by HCC are briefly discussed, with a review of the literature. GI bleeding secondary to involvement by HCC is rare. The enteric radiation injury seems to have been largely resposible for the GI bleeding in this patient.     

CASE REPORT: Radiotherapy in the treatment of duodenal bleeding due to hepatocellular carcinoma invasion

Haemorrhage from an hepatocellular carcinoma (HCC) directly invading the gastrointestinal (GI) tract is uncommon. A 58-year-old man was admitted with upper gastrointestinal (UGI) bleeding and panendoscopy on examination revealed a large duodenal ulcerative bleeding mass. The mass was eventually diagnosed as HCC by pathological examination. The bleeding failed to respond to conventional management of haemostasis, but resolved with an external beam of radiotherapy with a total dose of 6000 cGy over a 5 week period. This unusual presentation of UGI bleeding, due to HCC invading the duodenum and treated by radiotherapy, has not been previously reported.     

Recurrent fibrolamellar hepatocellular carcinoma with biliary invasion: Successful resection

A jaundiced 17-year-old man was diagnosed as having a local recurrence of fibrolamellar hepatocellular carcinoma 2 years and 4 months after left hepatic trisegmentectomy with total caudate lobectomy had been performed. The patient had a tumor occupying the upper part of the extrahepatic and intrahepatic bile ducts. Complete resection of the recurrent tumor was carried out. The patient remains well 3 years after the second surgery. Fibrolamellar hepatocellular carcinoma, a rare type of liver cancer, is a well defined disease entity with distinct clinical and histopathological features and a favorable prognosis. The good prognosis seems to warrant aggressive surgical intervention in patients with recurrences. Therefore, additional surgery for tumor recurrence should be considered. To our knowledge, this is the first report of a case in which a recurrent tumor of fibrolamellar hepatocellular carcinoma invaded the entire bile duct wall was successfully resected.     

小肝癌MR信号值与微血管侵犯相关性分析

目的分析小肝癌MR信号值与微血管侵犯(microvascular-invasion,MVI)的相关性。方法收集整理2010年12月至2019年1月解放军总医院第五医学中心小肝癌手术切除且于术前1周至1个月内行MR动态增强扫描检查的患者33例,根据病理诊断分为微血管侵犯组和非微血管侵犯组,进一步分为甲胎蛋白(AFP)阳性组和阴性组,测量并计算术前MR图像T1WI、T2WI、DWI序列及动态增强扫描动脉期、门脉期、延迟期病变信号值与相邻肝背景信号值的比值。结果33例患者中微血管侵犯22例,非微血管侵犯组11例;AFP阳性组17例,AFP阴性组16例。AFP阳性病例微血管侵犯与非微血管侵犯组间动脉期强化和延迟期强化信号特征差异有统计学意义(P<0.05),而T1WI序列、T2WI、DWI序列病变信号特征差异无统计学意义(P<0.05);AFP阴性病例T1WI序列、T2WI、DWI序列及动态增强扫描各期病变信号特征差异无统计学意义(P<0.05)。结论微小肝癌MR动态增强扫描病变强化特征可用于预测病变是否存在微血管侵犯。     

Histological evaluation of intracapsular venous invasion for discrimination between portal and hepatic venous invasion in hepatocellular carcinoma

Background and Aim:  Histological criteria for intracapsular venous invasion (IVI) that would allow its discrimination between portal and hepatic venous invasion in hepatocellular carcinoma (HCC) have not been established.
Methods:  We evaluated IVI immunohistochemically to discriminate between portal and hepatic venous invasion in 89 resected specimens from patients with HCC. IVI was defined as the microscopic involvement of the vessels within the fibrous capsule of HCC. The hepatic venous system was subdivided into the central vein and the sublobular/hepatic vein. Immunohistochemical analysis with the D2-40 monoclonal antibody revealed lymphatic vessels.
Results:  In non-neoplastic liver tissues, the portal veins ( n  = 4355) were accompanied by lymphatic vessels (99.7%), bile ductules (100%) and arteries (96%), whereas the central veins ( n  = 3932) and sublobular/hepatic veins ( n  = 662) were rarely accompanied by lymphatic vessels (0% and 17%, respectively) and bile ductules (12% and 33%, respectively). In total, 29 IVI foci were detected; three foci were clearly visible within vessels that contained a distinct layer of connective tissue fibers, signifying sublobular/hepatic venous invasion. As the remaining 26 foci were accompanied by lymphatic vessels (26/26 [100%]), bile ductules (21/26 [81%]) and arteries (10/26 [38%]), these foci were considered to reflect intracapsular portal venous invasion rather than venous invasion of the central vein. Intracapsular portal venous invasion was significantly associated with extratumoral portal venous invasion ( P  < 0.001).
Conclusions:  D2-40 immunoreactivity for the histological evaluation of IVI in HCC allows discrimination between portal and hepatic venous invasion for cases in which portal venous invasion predominates.     

Interobserver and intraobserver variability in evaluating vascular invasion in hepatocellular carcinoma

Background and Aim: Hepatocellular carcinoma (HCC) is unique in that the presence of vascular invasion significantly changes tumor stage. Even though searching for vascular invasion is a common practice in surgical pathology, there appears to be a great variation among pathologists in its recognition. This study was designed to assess whether HCC could be accurately staged using vascular invasion as a staging parameter. Methods: The interobserver and intraobserver agreement for vascular invasion was analyzed in 126 liver resections for HCC. Selected slides were circulated twice among six pathologists for independent review using their own criteria. One to three representative images from 26 equivocal cases selected by one of the authors were re‐evaluated by the pathologists. The presence or absence of vascular invasion on each slide or image was recorded as yes or no. The results were analyzed using unweighted kappa statistic analysis for multiple raters. Results: The interobserver agreement was moderate on two slide circulations with kappa values of 0.50 (95% confidence interval 0.45–0.55) and 0.43 (0.38–0.47), respectively. The kappa value dropped significantly to 0.19 (0.09–0.29) on selected images photographed from controversial cases. The intraobserver agreement was moderate, with kappa values ranging from 0.23 to 0.56 (mean = 0.45). Conclusions: Pathologists can reproducibly recognize vascular invasion in many HCC cases but may have difficulty in equivocal cases, which may lead to either understaging or overstaging of the tumors. This may have a significant impact on prognostic assessment and therapeutic decision making. Our observations indicate the need for improved definition for vascular invasion in HCC.     

Unusual cause of gastrointestinal bleeding in a cirrhotic patient:hepatocellular carcinoma with gastric invasion

BACKGROUND:Upper gastrointestinal(GI)bleeding is a common complication of portal hypertension in cirrhotic patients,and hepatocellular carcinoma(HCC)is the most common tumor in cirrhotic livers.Bleeding from tumor erosion into the GI tract is very rare.A patient with HCC and gastric tumor invasion was described and the previously reported cases were reviewed. METHOD:A patient with upper GI bleeding was treated in a tertiary hospital. RESULTS:A cirrhotic patient with a HCC invading the stomach leading to upp...     

Alpha-fetoprotein and tumour size are associated with microvascular invasion in explanted livers of patients undergoing transplantation with hepatocellular carcinoma

Background:

To determine factors associated with outcomes and microvascular invasion (MVI) in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC).

Methods:

Between July 1996 and August 2008 at the Universities of Kentucky or Tennessee, LT recipients were retrospectively analysed.

Results:

One hundred and one patients had HCC in the explanted liver; one patient was excluded because of fibrolamellar histology. Seventy-nine (79%) were male and 81 (81%) were older than 50. HCC was incidental in 32 patients (32%). Median follow-up was 31 months. Ten patients (10%) developed recurrence, which was associated with poor survival (P= 0.006). Overall 1-, 3-, and 5-year survival rates were 87%, 69% and 62%, respectively. Excluding patients with lymph node metastasis (LNM) or MVI yielded 91%, 81% and 75% survival at the same time points. MVI was independently associated with recurrence (OR 28.40, 95% CI 1.77–456.48, P= 0.018) and decreased survival (OR 4.70, 95% CI 1.24–17.80, P= 0.023), and LNM with decreased survival (OR 6.05, 95% CI 1.23–29.71, P= 0.027). Tumour size (OR 4.1, 95% CI 1.2–13.5, P= 0.013) and alpha-fetoproptein (AFP) > 100 (OR 5.0, 95% CI 1.4–18.1, P= 0.006) were associated with MVI.

Conclusions:

MVI greatly increases the risk of recurrence and death after LT for HCC, and is strongly associated with tumour size and AFP > 100.     

Combined AFP-CRUT with microvascular invasion accurately predicts mortality risk in patients with hepatocellular carcinoma following curative liver resection

Aims: To establish and validate an equation of α-fetoprotein (AFP) change rate over unit time (AFP-CRUT) as a potential predictor of survival after resection in patients with hepatocellular carcinoma (HCC). Methods: The AFP-CRUT was constructed based on dynamic variation in AFP over time and then categorized into quintiles. The area under the receiver operating characteristic (ROC) curve showed the performance for survival prediction. Results: As independent risk factors associated with mortality, microvascular invasion (MVI) (p = 0.003) and AFP-CRUT quintiles (p = 0.048) were combined to enhance the predictive effect. The highest 5-year overall survival rate following curative liver resection (93%) was observed in patients with MVI absent and AFP-CRUT in quintile 1 (49.64 to 209.61). In contrast, the lowest 5-year overall survival (7%) was obtained in quintile 5 (?469.29 to 6.45) with MVI present. In validation cohorts at both 12 and 24 months, AFP-CRUT performed well as a potential prognostic biomarker. Conclusions: Combining AFP-CRUT quintiles with MVI may predict significantly improved outcomes and enhance the predictive power for patient responses to therapeutic intervention.     

Reappraisal of repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion

Background and Aim:  This study aimed to evaluate the therapeutic efficacy and safety of repeated transarterial chemoembolization (TACE) with additional radiation therapy (RT) in hepatocellular carcinoma (HCC) with portal vein (PV) invasion.
Methods:  We performed survival analysis of consecutive HCC patients with PV invasion according to the treatment modalities after stratification by the degree of PV invasion and liver function retrospectively.
Results:  During 2005, 281 patients were newly diagnosed to have HCC with PV invasion at our institution. Repeated TACE or transarterial chemoinfusion (TACI) was performed in 202 (71.9%) patients and additional RT was performed for PV invasion in 43 of them. A total of 281 patients had a median survival of 5.2 months and a 2-year survival rate (YSR) of 19.2%. Repeated TACE showed significant survival benefits compared with conservative management in patients with PV branch invasion; median survival and 2-YSR was 10.2 vs 2.3 months and 33.7% vs 0% in Child–Pugh A categorized patients and 5.5 vs 1.3 months and 10.3 vs 0% in Child–Pugh B categorized patients, respectively ( P  < 0.001). In patients with PV branch invasion, the survival rate was significantly longer with TACE/TACI plus RT than with TACE/TACI alone both in Child–Pugh A categorized patients (1-YSR: 63.6 vs 35.6%, P  = 0.031) and Child–Pugh B categorized patients (1-YSR: 66.7 vs 7.7%, P  = 0.007). Repeated TACE was well tolerated in our patients, with only one dying within one month after TACE.
Conclusion:  Repeated TACE with additional RT can be performed safely and showed a significant survival benefit in HCC patients with PV branch invasion with conserved liver function.     

Endoscopic treatment of duodenal bleeding caused by direct hepatocellular carcinoma invasion with an ethanol injection

We report a case of a man who developed duodenal bleeding caused by direct hepatocellular carcinoma (HCC) invasion, which was successfully treated with endoscopic ethanol injection. A 57-year-old man with known HCC was admitted for melena and exertional dyspnea. He had been diagnosed with inoperable HCC a year ago. Urgent esophagogastroduodenoscopy (EGD) showed two widely eroded mucosal lesions with irregularly shaped luminal protruding hard mass on the duodenal bulb. Argon plasma coagulation and Epinephrine injection failed to control bleeding. We injected ethanol via endoscopy to control bleeding two times with 14 cc and 15 cc separately without complication. Follow-up EGD catched a large ulcer with necrotic and sclerotic base but no bleeding evidence was present. He was discharged and he did relatively well during the following periods. In conclusion, Endoscopic ethanol injection can be used as a significantly effective and safe therapeutic tool in gastrointestinal tract bleeding caused by HCC invasion.     

Predictive value of tumor markers in patients with recurrent hepatocellular carcinoma in different vascular invasion pattern

BACKGROUND: Four tumor markers for hepatocellular carcinoma(HCC), alpha-fetoprotein(AFP), glypican-3(GPC3), vascular endothelial growth factor(VEGF) and des-gammacarboxy prothrombin(DCP), are closely associated with tumor invasion and patient's survival. This study estimated the predictability of preoperative tumor marker levels along with pathological parameters on HCC recurrence after hepatectomy.METHODS: A total of 140 patients with HCC who underwent hepatectomy between January 2012 and August 2012 were enrolled. The demographics, clinical and follow-up data were collected and analyzed. The patients were divided into two groups: patients with macroscopic vascular invasion(Ma VI +) and those without Ma VI(Ma VI-). The predictive value of tumor markers and clinical parameters were evaluated by univariate and multivariate analysis.RESULTS: In all patients, tumor size(8 cm) and Ma VI were closely related to HCC recurrence after hepatectomy. For Ma VI+ patients, VEGF(900 pg/m L) was a significant predictor for recurrence(RR=2.421; 95% CI: 1.272-4.606; P=0.007). The 1- and 2-year tumor-free survival rates for Ma VI+ patients with VEGF ≤900 pg/m L versus for those with VEGF 900 pg/m L were 51.5% and 17.6% versus 19.0% and 4.8%(P0.001). For Ma VI- patients, DCP 445 m Au/m L and tumor size 8 cm were two independent risk factors for tumor recurrence(RR=2.307, 95% CI: 1.132-4.703, P=0.021; RR=3.150, 95% CI: 1.392-7.127, P=0.006; respectively). The 1- and 2-year tumor-free survival rates for the patients with DCP ≤445 m Au/m L and those with DCP 445 m Au/m L were 90.4% and 70.7% versus 73.2% and 50.5% respectively(P=0.048). The 1-and 2-year tumor-free survival rates for the patients with tumor size ≤8 cm and 8 cm were 83.2% and 62.1% versus 50.0% and 30.0%, respectively(P=0.003).CONCLUSIONS: The Ma VI+ patients with VEGF ≤900 pg/m L had a relatively high tumor-free survival than those with VEGF 900 pg/m L. In the Ma VI- patients, DCP 445 m Au/m L and tumor size 8 cm were predictive factors for postoperative recurrence.     

Gastrointestinal metastasis in hepatocellular carcinoma: radiological and endoscopic studies of 11 cases

BACKGROUND: From October 1990 to January 1999, 11 of 2237 hepatoma patients at our hospital had gastrointestinal tract metastasis. We describe the radiological and endoscopic features, clinical course and prognoses of those patients. METHODS: All patients were male. Six patients were hepatitis B carriers, and cirrhosis was noted in eight patients on admission. We reviewed all available radiological, endoscopic and pathological features. RESULTS: The commonest clinical presentation was frank gastrointestinal bleeding. Histological proof of gastrointestinal involvement was seen in six patients. Endoscopic features included ulcerative tumours mimicking advanced gastric carcinoma (43%) and submucosal tumours (29%). The sites of organ involvement were stomach (five), duodenum (two), colon (three) and duodenum and colon (one). Direct invasion by a contiguous neoplasm was the major route of gastrointestinal tract metastasis. Portal vein thrombosis may be the key point of haematogenous spread to other sites. CONCLUSIONS: The prognosis in these patients was extremely poor. Almost all patients died within 5 months if no further aggressive management was performed. Surgical intervention may be the optimal choice for palliative treatment of HCC with gastrointestinal tract involvement.     

Interstitial tumour cell invasion in small hepatocellular carcinoma. Evaluation in microscopic and low magnification views

In order to study the process of hepatocellular carcinoma (HCC) development, and to search for a clue to histologic diagnosis of well-differentiated HCC (wd-HCC), interstitial invasion in small HCC was evaluated. The study material consisted of 35 cases of HCC that were smaller than 3 cm that comprised 17 cases of wd-HCC, 18 cases of moderately or poorly differentiated classical HCC (cl-HCC), and 20 cases of large regenerative nodules (LRN). Interstitial invasion was microscopically classified into three patterns: (i) crossing type, in which HCC was invading across fibrous septa of tumour nodules; (ii) longitudinal type, in which tumour cells were growing longitudinally within fibrous septa; and (iii) irregular type, in which the portal area was irregularly invaded by HCC. The crossing type was found in two cases (12%) of wd-HCC and 10 cases (56%) of cl-HCC while the longitudinal type was observed in 16 cases (94%) of wd-HCC and eight cases (44%) of cl-HCC. The irregular type was frequently seen in wd-HCC (15 cases, 88%), and cl-HCC (12 cases, 67%). No interstitial invasion was observed in LRN. Interstitial invasion could be recognized even in the low magnification view of histological specimens, with a detection rate of 59% (10 cases) in wd-HCC and 72% (13 cases) in cl-HCC. These results suggest that evaluation of interstitial invasion is useful in diagnosing wd-HCC independent of cellular atypia. In addition, such invasive growth is revealed to play an important role in destroying original hepatic architecture during its developmental process from the early to advanced stages.