Portal venous tumor growth-type of hepatocellular carcinoma without liver parenchyma tumor nodules: a case report

The patient was a 43-year-old man with chronic hepatitis B without history of hepatocellular carcinoma (HCC), who was first diagnosed with thrombosis in right portal vein trunk and portal vein branches and ruptured esophageal varices in October 2011. He underwent endoscopic variceal ligation, but ruptured repeatedly. Despite anti-coagulant therapy, the thrombosis expanded from right portal vein trunk to upper mesenteric vein in March 2012. Computed tomography (CT) scan showed that portal vein thrombosis had low density from early to late phase. No focal liver lesions were identified by CT scan or ultrasound, and alpha-fetoprotein (AFP) was within normal range. He died by intractable esophageal variceal bleeding in April 2012. Pathological examination of autopsy specimen showed that portal vein thrombosis was consistent with poorly-differentiated HCC. The portal vein tumor thrombosis (PVTT) had only a few tumor vessels, which were compressed by fibromatous change originating from HCC formation, so were represented as low-density lesions from arterial to portal phase of CT. In addition, PVTT was negative for AFP, so representing serum value of AFP within normal range. PVTT had positive staining for c-kit, which is a liver stem cell marker. Liver tumors in the whole liver parenchyma were not found pathologically. PVTT might have the characteristics of presumed liver cancer stem cells. We experienced the first case of HCC only in portal vein without liver parenchyma tumor nodules, with difficult differential diagnosis from a non-malignant portal vein thrombosis. We also reported new tumor profiles of the portal venous tumor growth- type of HCC.     

Complete remission of hepatocellular carcinoma with portal vein tumor thrombus and lymph node metastases by arterial infusion of 5-fluorouracil and interferon-α combination therapy following hepatic resection

We report two cases of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) and lymph node (LN) metastases successfully treated by hepatic arterial infusion of 5-fluorouracil (5-FU) combined with systemic injection of interferon (IFN)-α following hepatic resection for the liver tumor. Complete remission was obtained. Case 1 was a 51-year-old man who had HCC in the right lobe of the liver with PVTT and multiple intrahepatic metastases. He also had abdominal and mediastinal LN metastases. Case 2 was a 53-year-old man who had diffuse-type HCC in the right lobe of the liver with PVTT and intrahepatic metastases. A chest computed tomography scan revealed lymph nodes enlarged to 1.0 cm from the mediastinum to the left supraclavicular space. Both patients underwent the hepatectomy to reduce the tumor volumes and remove the PVTT to relieve portal vein obstruction. Following the surgery, the patients underwent IFN-α/5-FU combination therapy. Three months after this combined therapy, tumor markers (both α-fetoprotein and protein induced by vitamin K absence or antagonist II) returned to the normal range and residual tumors in the liver disappeared. The patients are alive without any recurrence more than 1 year after initial treatment. IFN-α/5-FU combined therapy following hepatic resection is a promising modality for the treatment of advanced HCC with LN metastasis.     

Treatment of colorectal liver metastasis with biliary and portal vein tumor thrombi by hepatopancreatoduodenectomy

We present a case of a large colorectal liver metastasis with portal vein and biliary tumor thrombi and duodenal and jejunal direct invasion that required hepatopancreatoduodenectomy. A 38-year-old woman presented to her local hospital with right back pain and jaundice. She had undergone transverse colectomy and limited liver resection for transverse colon cancer with a synchronous liver metastasis in September 1991, and low anterior resection for rectal carcinoma in January 1996. She was diagnosed as having colorectal liver metastasis and was referred to our hospital for possible surgery. Radiologic and endoscopic examinations revealed a large liver tumor occupying the right lobe, biliary dilation in the left lateral section, and a portal vein tumor thrombus. Invasion of the inferior vena cava and the right renal vein were also suspected. Intraoperative findings revealed a large liver tumor that occupied the right lobe and invaded the duodenum and jejunum. The tumor was resected successfully by right trisectionectomy, caudate lobectomy, pancreatoduodenectomy, partial resection of the jejunum, and combined portal vein resection and reconstruction. The inferior vena cava, right kidney, and renal vein could be detached from the tumor. The patient has enjoyed an active life without recurrence for 2 years since the operation.     

超声造影在原发性肝癌切除术中的应用(附42例报告)

目的探讨超声造影在原发性肝癌切除术中的价值。方法收集本院肝胆外科2010年1月至2011年12月收治的术中采用超声造影指导行肝切除术的病例资料,共计42例,将其在肝癌切除术中超声造影检查发现的病灶数目、大小、与肝内管道的关系等与术前超声、CT、术中超声发现的病灶的数目、大小、与肝内管道的关系等进行比较。结果术中超声造影检查除发现术前超声、CT等影像学检查发现的阳性病灶外,术中超声造影还能更准确的判断肝内病灶的数目、性质和病灶与肝内管道的关系等,更清楚显示了主病灶的卫星结节8例;新发现门脉癌栓共6例,其中主干2例,门脉左支1例,门脉右支3例。发现胆总管癌栓2例、下腔静脉癌栓1例;发现3例远离原病灶的小病灶(约0.5 cm)。结论在原发性肝癌切除术中超声造影能发现残留病灶,避开重要的解剖结构,有重要的应用价值。     

Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To analyze hepatocellular carcinoma(HCC) patients with portal vein tumor thrombosis(PVTT) using the tumor-node-metastasis(TNM) staging system.METHODS: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009.We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system(7th edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center.Portal vein invasion(vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein,vp2 as an invasion or tumor thrombus in the second branch of the portal vein,vp3 as an invasion or tumor thrombus in the first branch of the portal vein,and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side.RESULTS: The cumulative 5-year overall survival(5yr OS) and 5-year disease-free survival(5yr DFS) rates of the 372 patients were 58.3% and 31.3%,respectively.The 5yr DFS and 5yr OS of vp3-4 patients(n = 10) were 20.0%,and 30.0%,respectively,which was comparable with the corresponding survival rates of vp1-2 patients(P = 0.466 and 0.586,respectively).In the subgroup analysis of patients with macroscopic PVTT(vp2-4),the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not(P = 0.747).There was a significant difference in the DFS between patients with stage Ⅰ HCC and those with stage Ⅱ HCC(5yr DFS 39.2% vs 23.1%,P 0.001); however,theDFS for stage Ⅱ was similar to that for stage Ⅲ(5yrD FS 23.1% vs 13.8%,P = 0.330).In the subgroup analysis of stage Ⅱ-Ⅲ HCC(n = 148),only alpha-fetoprotein(AFP) 100 mg/dL was independently associated with DFS.CONCLUSION: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2.AFP stratified the stage Ⅱ-Ⅲ HCC patients according to prognosis.     

Hepatocellular Carcinoma With Tumor Thrombus Occupying the Right Atrium and Portal Vein: A Case Report and Literature Review

Hepatocellular carcinoma (HCC) patients with tumor thrombus extended through the major hepatic veins and inferior vena cava into the right atrium (RA) are rare, and most cases are considered as the advanced stage with a poor prognosis.We report a case of HCC with a tumor thrombus extending into the RA and a tumor thrombus in the portal vein. A literature search for case reports was performed on PubMed.Compared with the published literature, our case is one of the youngest patients, but with the most advanced HCC that invades both the hepatic inflow and outflow vasculature. For this patient, we resected the tumor thrombus in the RA with the use of cardiopulmonary bypass, and then removed the tumor thrombus in the portal vein and ligated the left branch of portal vein. Because of insufficient remnant liver volume, microwave ablation and transcatheter arterial chemoembolization were performed to control the growth of HCC. The patient survived 6 months after surgery.This case suggests that for patients with extension of HCC into the RA and portal vein, surgery is a useful therapeutic modality, even in case that liver tumor cannot be resected.     

Adenosquamous carcinoma of the gallbladder with tumor thrombus in left portal trunk

We report a surgically resected case of adenosquamous carcinoma of the gallbladder accompanied by portal tumor thrombosis, which is regarded as a rare complication. A 73-year-old man was admitted to our hospital because of epigastralgia. Preoperative examinations led to a diagnosis of advanced gallbladder carcinoma with liver metastasis, and operation was performed. Since intraoperative ultrasonography showed a tumor thrombus in the left main portal trunk originating from the metastatic lesion in the left medial segment of the liver, extended left lobectomy with extrahepatic bile duct resection and lymph node dissection was performed, instead of right trisegmentectomy, as proposed preoperatively. Histological examination revealed adenosquamous carcinoma of the gallbladder with medullary growth that was similar to the hepatocellular carcinoma, most notably in the metastatic lesion of the liver and in the portal tumor thrombus. We discuss the relation between portal tumor thrombosis and medullary tumors, and note the atypical operative method employed.     

Isolated metastasis to the gallbladder from hepatocellular carcinoma

Aim: Metastasis to gallbladder (GB) from hepatocellular carcinoma (HCC) is rare, and it is difficult to determine indications for surgery. We report eight cases of synchronous isolated GB metastasis, and analyze their features retrospectively. Methods: Among 439 HCC patients who underwent hepatectomy from 1998 to 2008 at our institution, 393 (89.5%) underwent concurrent cholecystectomy. Results: Among them, eight (1.8%) had GB metastasis without other distant metastases. None of these cases showed evidence of direct invasion. All cases had advanced portal vein thrombus (PVTT) and their main tumor located near the GB bed. Five cases had apparent tumor mass in the GB wall, and the other three cases had only tumor thrombus in the GB veins. Six cases were treated postoperatively with local infusion therapy with interferon, and three of them showed long‐term survival. Conclusion: Our eight cases of GB metastasis from HCC were closely related to PVTT. Surgical resection and multimodal treatment would be necessary for long‐term survival in cases with isolated GB metastasis.     

Venous tumor thrombosis and cavernous transformation of the portal vein in a patient with gastric carcinoma

A case of extensive extra-and intrahepatic portal tumor thrombosis, with no metastatic foci in liver parenchyma, secondary to advanced gastric carcinoma in a 69-year-old man is reported. The portal tumor thrombosis was characterized by enlargement of the thrombosed segment of the vein, decreased density mass without intraluminal enhancement of the involved vein, nonvisualization of the portal venous branch in the involved lobe, and the so-called cavernous transformation of the portal vein. The surgically resected gastric specimen showed Borrmann type 3 advanced papillary adenocarcinoma. The portal tumor thrombus is presumed to have arisen from vascular invasion in the primary foci of gastric carcinoma, and then to have permeated the portal vein without invasion of liver parenchyma.     

Surgical treatment for hepatocellular carcinoma with portal vein tumor thrombus

BACKGROUND/AIMS: To study the value of surgical treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODOLOGY: From January 1997 to December 2001, 63 cases of HCC with portal vein tumor thrombus underwent liver resection combined with PVTT removal (group 1). Between December 2001 and December 2003, 20 patients received adjuvant portal vein chemotherapy (PVC) after the surgical procedures mentioned above (group 2). Treatment outcome and the surgical features in these two groups were studied. RESULTS: The median overall survival in group 2 was significantly longer than that in group 1 (10.9 months vs. 7.8 months, p < 0.05). There were significant differences between the survival of the two groups (log-rank, p < 0.05). In group 1 the 1-, 3-, and 5-year survival rates were 18.0%, 14.8% and 1.6%, respectively. In group 2 the 1-year survival rate was 30%. CONCLUSIONS: Liver resection combined with PVTT removal and the postoperative PVC is beneficial to the survival of HCC patients with PVTT. Postoperative PVC might enhance the effect of these surgical approaches.     

Hepatic resection for hepatocellular carcinoma based on tumor hemodynamics

Survival or disease‐free survival is not considered an appropriate surrogate outcome for the locoregional curability (i.e. surgical margin) of hepatectomy for hepatocellular carcinoma because these are greatly influenced by non‐metastatic factors like multicentric carcinogenesis (MC) or liver function. Hepatocellular carcinoma metastasizes by hematogenous seeding; therefore, the tumor blood flow (TBF) drainage area is a high‐risk area for intrahepatic metastasis, and can be identified by computed tomography under hepatic arteriography and completely resected as part of the surgical margin. The TBF pattern is classified into marginal, portal vein or hypovascular types. Partial hepatectomies were mostly performed in patients with marginal or hypovascular type, whereas anatomical surgery was frequently performed in those with portal vein type. Pathologically, nodules inside the TBF drainage area were moderately or poorly differentiated carcinomas, suggesting intrahepatic metastasis. In contrast, those outside the drainage area were frequently solitary and contained well‐differentiated carcinoma, which is consistent with MC. The pattern of tumor recurrences after TBF‐based hepatectomy is divided into two distinct groups – “a few nodules” and “many nodules in multiple segments or extrahepatic” – indicating that intrahepatic recurrences develop from MC and from circulating tumor cells in peripheral blood, respectively. Anatomical resection has not shown a survival benefit over that of TBF‐based partial hepatectomy. TBF‐based hepatectomy enables us to preserve liver function without compromising locoregional curability.     

Pathological Complete Remission of Advanced Hepatocellular Carcinoma with Main Portal Vein Tumor Thrombosis by Hepatic Arterial Infusion Chemotherapy

Cures for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) are rare and difficult. We report a case of pathologically confirmed complete remission of HCC induced by hepatic arterial infusion chemotherapy (HAIC). A 45-year-old male patient had a massive HCC in the right lobe of the liver and tumor thrombus in the right and main portal veins. He achieved a partial response after two cycles of HAIC with 5-fluorouracil (750 mg/m²) and cisplatin (25 mg/m²). After the completion of six cycles he received a curative partial hepatectomy, and histopathology revealed complete necrosis without any viable tumor cell. He was in good health at a 4-month follow-up. These results suggest that this regimen is a promising therapeutic modality for the treatment of advanced HCC with PVTT.     

Two-stage liver surgery for advanced liver metastasis synchronous with colorectal tumor

BACKGROUND/AIMS: To evaluate the efficacy of two-stage surgery and multidisciplinary approach, in the treatment of primary colorectal cancer, synchronous with advanced liver metastases. METHODOLOGY: Sixty-two patients who underwent two-stage surgery for advanced metastatic liver disease synchronous with colorectal tumor were studied. In the first-stage surgery, the primary colorectal tumor was resected. Depending on the location of the main tumor mass, ligation and transection of the relevant (right or left) main portal vein branch was done. Subsequently, the metastatic nodules in the contralateral lobe were ablated by microwave therapy. An arterial jet port catheter was also introduced into the hepatic artery via the gastroduodenal artery for locoregional chemoimmunotherapy. Two days after the first-stage surgery locoregional transarterial targeting chemoimmunotherapy was given. The second-stage hemihepatectomy was carried out forty to forty-five days after the initial surgery. As an adjuvant treatment locoregional targeting chemoimmunotherapy was carried out in all patients via the arterial chemoport. RESULTS: Mean survival was 66+/-4 months. There were no operative deaths. CONCLUSIONS: Two-stage liver surgery including, portal vein branch ligation, microwave ablative therapy and transarterial targeting locoregional chemoimmunotherapy is the best treatment for advanced, synchronous metastatic liver disease of colorectal origin. It results in an increase in the overall survival of these patients with good postoperative quality of life, which encourages the hepato-biliary surgeon to venture upon this herculean task thus increasing the resectability rate of the tumor.     

Macroscopic portal vein tumor thrombi of liver metastasis from colorectal cancer

We present a case of multiple colorectal liver metastases with macroscopic portal vein thrombi. A 55-year-old woman presented to us with rectosigmoid cancer and presented with two liver metastases. The tumor in the posterior sector was associated with invasion of first order branches of the portal vein. We performed low anterior resection, hepatic posterior sectorectomy and partial left anterior sectorectomy. Both the colorectal cancer and liver tumors exhibited histological characteristics of moderately differentiated adenocarcinoma with a substantial amount of mucin production. The liver metastases were associated with prominent tumor thrombi in many branches of the portal vein. Stronger staining for endoglin (CD 105) than for Fas ligand (Fas L) and matrix metalloproteinase (MMP-2) was observed in both the colorectal cancer and metastatic liver tumor cells. Expression of the vascular endothelial growth factor within the tumor cells was seen in both the colorectal cancer as well as the metastatic liver tumor cells. Six months after the operation, she was diagnosed to have multiple, more than about 20 liver metastases, and in 9 months after the operation, the patient died. The colorectal cancer with liver metastases associated with portal vein tumor thrombosis was poor prognosis, found neoplastic microvessel formation.     

A case of hepatocellular carcinoma with multiple lung, spleen, and remnant liver metastasis successfully treated by combination chemotherapy with the novel oral DPD-inhibiting chemotherapeutic drug S-1 and interferon-α

A 54-year-old man was admitted Osaka University Hospital for hepatocellular carcinoma (HCC) with portal vein thrombus and multiple intrahepatic metastases that extended to the bilateral lobes of the liver. He underwent multimodal therapy, including extended left lobectomy followed by intra-arterial 5-fluorourcil (5-FU) infusion chemotherapy combined with subcutaneous interferon-α (IFN-α) to treat the lesions in the residual liver. Seven months after the initial resection, recurrent tumors in the spleen, lung, and residual liver were detected by follow-up examination. We started a new regimen of per oral administration of S-1 and subcutaneous IFN-α injection, because the combined therapy with intra-arterial 5-FU infusion was not considered effective for distant metastases. After two cycles of S-1 and IFN-α, the metastatic tumor in the spleen and the recurrence in the residual liver had disappeared, and the diagnosis was complete remission with no adverse effect; the pulmonary metastasis showed a partial response, and was finally resected. This patient is still alive with no recurrence 32 months after initial hepatic resection. This outcome suggests that combination therapy with S-1 and IFN-α may be a promising treatment modality against advanced HCC with distant metastasis.     

Treatment of portal vein tumor thrombus using ~(125)Iodine seed implantation brachytherapy

We reported two cases of liver metastasis with portal vein tumor thrombus that developed after liver transplantation for hepato cellular carcinoma (HCC). Both the patients were women aged 43 and 55 years, who had liver metastasis and portal vein tumor thrombus formation after liver transplantations for HCC. For the treatment of portal vein tumor thrombus, 125I seeds were implanted into the hepatic tissue under the guidance of preoperative computed tomography (CT) images with a total radiation dose of 130 Gy...     

Successful preoperative treatment for hepatocellular carcinoma with tumor thrombus in the major portal branch by three-dimensional conformal radiation therapy--two case reports

The prognosis of hepatocellular carcinoma (HCC) patients with tumor thrombus in the main portal branch (PVTT) is very poor and a standard treatment regimen for HCC with PVTT has not yet been established. Therefore, a new strategy is necessary to control the patients of HCC with PVTT. Conventional radiation therapy for HCC was not effective because of low liver tolerance. On the other hand, because three-dimensional conformal radiation therapy (3D-CRT) can focus high-dose irradiation on a small area, we tried it for patients with PVTT as the preoperative adjuvant treatment. 3D-CRT which targeted the PVTT was performed for two HCC patients with PVTT before radical hepatectomy. Treatment schedules of 3D-CRT were as follows: in Case 1, the daily fraction size was 3 Gy, given five times per week, and the total dose was 39 Gy. In Case 2, the daily size was 6 Gy and the total dose was 60 Gy. Three or four weeks after 3D-CRT, the main tumor and PVTT were completely removed. On histological examination, the PVTT showed complete necrosis in Case 1, and 60% necrosis in Case 2. No serious complications occurred, and there have been no recurrences for more than one year after surgery in both cases. 3D-CRT targeting the PVTT may be promising as a preoperative adjuvant therapy for HCC with PVTT.     

Anatomic resection of segments 5, 6 and 7 of liver for hepatocellular carcinoma: prior control of right paramedian Glisson

Anatomic resection is theoretically effective in eradicating intrahepatic metastasis of hepatocellular carcinoma (HCC). In patients who undergo a larger volume of hepatectomy or who have hepatic dysfunction, the extent of hepatectomy is limited to avoid postoperative hepatic failure. In the present case, a limited anatomic resection according to Couinaud's segment was performed because of the large volume of the right hemi-liver. A 62-year-old male was found to have a 12-cm HCC in segments 5, 6 and 7, with alcoholic liver disease. The total liver function was Child-Pugh grade A, as indocyanine green retention rate at 15 minutes (ICGR15) was 12%. The resected liver volume of right hemihepatectomy estimated by CT volumetry was 72% and the permitted resected volume based on Takasaki's formula applying ICGR15 was 65%. As the portal branches of segment 8 was free from HCC involvement and the estimated volume of segments 5, 6 and 7 was 51%, we scheduled anatomic resection of these segments to secure remnant liver function. Under Pringle's maneuver, hepatic transection on the border between right and left liver was performed and the right paramedian Glisson's pedicle was exposed in the first step. Branches of segment 5 were divided and the border between segments 5 and 8 was confirmed. Then, the right lateral sector was resected and the right hepatic vein draining segment 8 was secured. Postoperative course was satisfactory and the patient was free from tumor relapse for 16 months after hepatectomy. Under a balance between tumor location and hepatic functional reserve, anatomic resection would be necessary for the treatment of HCC patients.     

The impact of sphingosine kinase 1 on the prognosis of hepatocellular carcinoma patients with portal vein tumor thrombus

Background. Though there is considerable evidence that sphingosine kinase 1(SPHK1) plays a key role in hepatocellular carcinoma(HCC) progression, the prognostic value of SPHK1 expression in HCC with portal vein tumor thrombus (PVTT) remains unclear.Aims. The purpose of this study was to investigate the relationship of SPHK1 expression with PVTT and HCC recurrence after hepatectomy.Methods. After screening of gene expression profiling of tumor cell lines, real-time PCR and immunohistochemistry were used to investigate the SPHK1 expression in PVTT and HCC samples. The clinical data of 199 HCC patients with nonmain PVTT who underwent liver resection with curative intention were studied.Results. We identified SPHK1 as the most over-expressed gene in PVTT via gene expression profiling of one human PVTT cell line (CSQT-2). SPHK1 expression was an independent factor affecting survival (hazard ratio [HR] 1.799, 95% confidence interval [CI] 1.337-2.368, P < 0.001) and tumor recurrence (HR 1.451, 95% CI 1.087-1.935, P = 0.011). Patients with SPHK1 over-expression had a poorer prognosis than those with SPHK1 under-expression (P < 0.001 and P = 0.011 for survival and tumor recurrence).Conclusions. SPHK1 might represent a novel and useful prognostic marker of HCC progression in patients with PVTT.     

Spontaneous regression of diffuse intrahepatic recurrence with portal vein tumor thrombus after resection of hepatocellular carcinoma

We report a rare case of spontaneous regression of diffuse intrahepatic recurrence with portal vein tumor thrombus (PVTT) after resection of hepatocellular carcinoma (HCC). A 68-year-old man with hepatitis C virus-related liver cirrhosis presented with a 40 mm tumor in the right anterior segment of the liver. The tumor was diagnosed as HCC by typical imaging findings and elevated serum alpha-fetoprotein (AFP) (716 ng/ml) and protein induced by vitamin K absence II (PIVKA II) (8,100 ng/ml). A right anterior sectionectomy of the liver was performed. Microscopically, the tumor was moderately differentiated HCC. Four months after resection, a computed tomography (CT) scan showed diffuse intrahepatic recurrence with PVTT. Serum AFP was 12,319 ng/ml and PIVKA II was 168,000 ng/ml. The patient did not receive any further treatment for HCC including herbal medicine, and stopped smoking. Two years and 5 months later, no lesion was detected on a CT scan when serum AFP was 1.9 ng/ml. Ischemia due to main portal vein occlusion and rapid tumor growth might have induced tumor regression in the present case. Moreover, abstention from smoking might have improved his immunological function.