Yuko Takami

Small-Cell Carcinoma of the Gallbladder: Report of a Case

Abstract: We report herein the case of an 81-year-old woman in whom a mass in the gallbladder was revealed by an ultra-sound examination conducted as part of a follow-up study for a silent gallstone. The mass showed evidence of invasion into the adjacent liver parenchyma. Under the tentative diagnosis of malignant neoplastic disease originating in the gallbladder, a cholecystectomy with partial hepatectomy was performed. Histological examination of the tumor confirmed a diagnosis of small-cell carcinoma of the gallbladder, which is considered to be a rare type of neoplasm.

Validity of FibroScan values for predicting hepatic fibrosis stage in patients with chronic HCV infection

OBJECTIVE:  The aim of this study was to validate the FibroScan system compared with liver histology and serum markers for the diagnosis of hepatic fibrosis. We also tried to determine the cut‐off levels and assess the feasibility of using FibroScan values to predict the fibrosis stage.

Intrahepatic cholangiocarcinoma with extensive sarcomatous change: Report of a case

A 77-year-old woman was admitted to our hospital with severe upper abdominal pain. Ultrasonography showed a well-defined hypoechoic mass with heterogeneity in the left lobe of the liver, and computed tomography demonstrated a low-density mass with enhanced peripheral areas. Magnetic resonance imaging revealed a mass with iso- to low signal intensity on T1-weighted images (WI) and heterogeneous high and low signal intensity on T2 WI. The tumor was found to be hypovascular by angiography. During 5 months of observation, the tumor increased in size, which strongly suggested malignancy. A laparotomy was performed under the provisional diagnosis of a neoplasm other than hepatocellular carcinoma, revealing that the hepatic mass had invaded the gastric wall. Therefore, a left hepatic lobectomy with dissection of the lymph nodes and hemigastrectomy was carried out. Histologically, the tumor was found to be composed of a large amount of sarcomatous elements and a small amount of adenocarcinomatous elements, both of which were partly intermingled. Immunohistochemically, the sarcomatous element demonstrated the features of malignant fibrous histiocytoma (MFH). Thus, a diagnosis of intrahepatic cholangiocarcinoma with MFH-like sarcomatous change was confirmed.

The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased in Kyushu area

Summary Background The incidence of hepatocellular carcinoma (HCC) in Japan has still been increasing. The aim of the present study was to analyze the epidemiological trend of HCC in the western area of Japan, Kyushu. Material/Methods A total of 10,010 patients with HCC diagnosed between 1996 and 2008 in the Liver Cancer study group of Kyushu (LCSK), were recruited for this study. Cohorts of patients with HCC were categorized into five year intervals. The etiology of HCC was categorized to four groups as follows; B: HBsAg positive, HCV-RNA negative, C: HCV-RNA positive, HBsAg negative, B+C: both of HBsAg and HCV-RNA positive, nonBC: both of HBsAg and HCV-RNA negative. Results B was 14.8% (1,485 of 10,010), whereas 68.1% (6,819 of 10,010) had C, and 1.4% (140 of 10,010) had HCC associated with both viruses. The remaining 1,566 patients (15.6%) did not associate with both viruses. Cohorts of patients with HCC were divided into six-year intervals (1996–2001 and 2002–2007). The ratio of C cases decreased from 73.1% in 1996–2001 to 64.9% in 2002–2007. On the other hand, B and -nonBC cases increased significantly from 13.9% and 11.3% in 1996–2001 to 16.2% and 17.6% in 2002–2007, respectively. Conclusions The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased after 2001 in Kyushu area. This change was due to the increase in the number and proportion of the HCC not only nonBC patients but also B patients.

Efficacy of surgical treatment using microwave coagulo-necrotic therapy for unresectable multiple colorectal liver metastases

Background Five or more colorectal liver metastases (CRLM) are considered marginally resectable and cannot be treated solely by hepatic resection (Hr). This study investigated the long-term effectiveness of surgical treatment using microwave coagulo-necrotic therapy (MCN) and/or Hr for marginally resectable or unresectable multiple CRLM. Methods This study retrospectively analyzed 82 consecutive CRLM patients with ≥5 CRLM who underwent MCN, Hr, or both, at our institution from 1994 to 2012. Presuming all CRLM were resected curatively, virtual remnant liver volume was calculated using preoperative computed tomography or magnetic resonance imaging. Virtual remnant liver volume <30% was defined as unresectable. Patients were divided into marginally resectable (Group Y; n=29) and unresectable (Group N; n=53). Overall and recurrence-free survival were assessed. Results Mean maximum tumor diameter and tumor number were 3.1 and 6.0 cm in Group Y and 3.3 and 11.3 cm in Group N. Surgical methods included MCN (n=16), MCN+Hr (n=9), and Hr (n=4) in Group Y, and MCN (n=28) and MCN+Hr (n=25) in Group N. One- and 2-year recurrence-free survival rates were 38.0% and 22.8% in Group Y, and 18.9% and 3.8% in Group N (P=0.01). However, 1-, 3-, and 5-year overall survival rates of Group N (86.8%, 44.6%, and 33.7%, respectively) were similar to those of Group Y (82.8%, 51.4%, and 33.3%, respectively; P= not significant each). Conclusion MCN may improve survival for patients with unresectable multiple CRLM, similar to that in patients with marginally resectable multiple CRLM.

Adenocarcinoma of the liver with osteoclast-like giant cells

To the Editor: A giant cell tumor of the bone is a common tumor characterized by proliferation of giant cells, which are surrounded by mononuclear cells. Osteoclast-like giant cell tumors (OCGTs), histologically similar to giant cell tumors of bone, have been described in several extraskeletal sites. There have been at least 40 reports describing approximately 60 occurrences of OCGTs in the pancreas, whereas only 16 liver tumors have been reported. In the present study, the clinicopathological characteristics of an adenocarcinoma of the liver with osteoclast-like giant cells (OCGCs) were examined. A 73-year-old woman presented at a neighborhood clinic with right hypochondrial pain of 3 months. A computed tomography (CT) scan revealed multilocular cystic lesions with a 14-cm diameter that occupied the right hepatic lobe. Iodine contrast further revealed a heterogeneously delayedenhanced solid component in the multilocular cystic lesion that had partially invaded the septum of cysts. The connection between cystic components and intrahepatic bile ducts was not evident in the magnetic resonance imaging (MRI) or magnetic resonance cholangiopancreatography. Further extensive diagnostic procedures showed no evidence of another tumor or metastases. Laboratory examinations revealed elevated levels of carcinoembryonic antigen (CEA; 218.3 ng/mL), CA19-9 (14 132 IU/mL), and DUPAN-2 (550 IU/mL), whereas the levels of α-fetoprotein (AFP; 3.7 ng/mL) and the protein induced by vitamin-K absence II (PIVKA-II; 12 mAu/mL) increased. Tests for hepatitis B surface antigen and hepatitis C virus antibody were negative. As preoperative examinations indicated that the tumor in the liver was the primary occurrence, a curative extended right hepatectomy was performed. Pathological gross findings revealed that the tumor in the right liver measured 145 × 83 mm and consisted of cystic portions containing mucinous fluid with or without hemorrhages and whitish solid portions located among or adjacent to the cysts (Fig. 1a). The tumor showed invasive growth into non-tumorous areas of the liver. Microscopic findings revealed that the tumor consisted of two distinct histological components (e.g. an adenocarcinoma and pleomorphic mononuclear cell component). The adenocarcinoma mainly lined the cystic lesions forming irregular papillae or fused glands (Figs 1b,2a). Nuclear atypia was evident and cellular polarity was disturbed. In addition, invasive proliferation was observed with a MIB-1 index of 20%.

The Efficacy of Continued Sorafenib Treatment after Radiologic Confirmation of Progressive Disease in Patients with Advanced Hepatocellular Carcinoma

Background Whether radiologically detected progressive disease (PD) is an accurate metric for discontinuing sorafenib treatment in patients with hepatocellular carcinoma (HCC) is unclear. We investigated the efficacy of sorafenib treatment after radiologic confirmation of PD in patients with advanced HCC. Methods We retrospectively analyzed HCC patients treated with sorafenib at Kyushu Medical Center. Six of the 92 patients with radiologically confirmed PD were excluded because they were classified as Child-Pugh C or had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3; 86 patients were ultimately enrolled. Results Among the 86 patients, 47 continued sorafenib treatment after radiologic confirmation of PD (the continuous group), whereas 39 did not (the discontinuous group). The median survival time (MST) in the continuous group after confirmation was 12.9 months compared with 4.5 months in the discontinuous group (p <0.01). The time to progression in the continuous group after confirmation was 2.6 months compared with 1.4 months in the discontinuous group (p <0.01); it was 4.2 months and 2.1 months in patients who had received sorafenib ≥4 months and <4 months, respectively, before confirmation (p = 0.03). In these subgroups, the post-PD MST was 16.7 months and 9.6 months, respectively (p < 0.01). Independent predictors of overall survival after radiologic detection of PD were (hazard ratio, confidence interval): ECOG PS <2 (0.290, 0.107–0.880), Barcelona Clinical Liver Cancer stage B (0.146, 0.047–0.457), serum α-fetoprotein level ≥400 ng/mL (2.801, 1.355–5.691), and post-PD sorafenib administration (0.279, 0.150–0.510). Conclusion Continuing sorafenib treatment after radiologic confirmation of PD increased survival in patients with advanced HCC. Therefore, radiologically detected PD is not a metric for discontinuation of sorafenib treatment in such patients.

Anterior approach for right hepatectomy with hanging maneuver for hepatocellular carcinoma: a multi-institutional propensity score-matching study

This multi‐institutional study aimed to assess the benefits of anterior approach for right hepatectomy with hanging maneuver (ARH‐HM) for hepatocellular carcinoma (HCC) compared with conventional right hepatectomy (CRH).

Long-Term Maintenance of Complete Response after Sorafenib Treatment for Multiple Lung Metastases from Hepatocellular Carcinoma.

Sorafenib is an effective treatment for unresectable hepatocellular carcinoma (HCC) characterized by disease stabilization. However, the response rates are very low (<9%), and a complete response is rarely achieved. We report an extremely rare case of a HCC patient with multiple lung metastases treated with sorafenib who achieved a complete response for a long period. A 77-year-old woman was diagnosed with chronic hepatitis C in 1990. In 2007, a HCC detected in the liver was treated with percutaneous ethanol injection therapy. Subsequently, recurrence of HCC in the liver was treated with microwave coagulonecrotic therapy in 2010. In April 2011, a computed tomography (CT) scan revealed innumerable multiple metastases spread diffusely in both lungs. Tumor marker levels were extremely high [α-fetoprotein (AFP) 76,170 ng/ml, lens culinaris agglutinin-reactive fraction of AFP 7.5%, des-γ-carboxyprothrombin (DCP) 63,400 mAU/ml]. Sorafenib was administered at a reduced dose of 400 mg/day because of old age. Four months after sorafenib treatment, AFP and DCP had decreased to within normal levels, and the multiple lung metastases had disappeared. Currently, sorafenib is administered at a reduced dose of 400 mg/day, and the complete response has been maintained for 48 months.

The Safety and Efficacy of Combination Therapy of Sorafenib and Radiotherapy for Advanced Hepatocellular Carcinoma: A Retrospective Study

Objective Sorafenib is a standard therapy for advanced hepatocellular carcinoma (HCC), whereas radiotherapy is effective for local control of extrahepatic spread (EHS) or macrovascular invasion (MVI). This study investigated the safety and efficacy of this combined therapy to treat advanced HCC. Methods This retrospective study reviewed 62 patients with advanced-stage HCC with EHS or MVI who received sorafenib therapy, excluding the patients with only lung metastases. Results Of the 62 patients, 15 were treated using the combined therapy of sorafenib and radiotherapy (group RS), and 47 were treated with sorafenib monotherapy (group S). In group RS, patients were treated using three-dimensional conformal radiotherapy with a total irradiation dose of 30-60 Gy (median, 50 Gy). Irradiation was targeted at the bone, lymph nodes, adrenal gland, and MVI in 6, 5, 1, and 4 patients, respectively. The overall incidence of adverse events was 93.3% in group RS and 91.5% in group S (p=N.S.). Incidences of thrombocytopenia, leukopenia, and skin reaction were significantly higher in group RS (73.3%, 40.0%, and 66.7%, respectively) than in group S (36.2%, 10.6%, and 27.7%, respectively, p=0.02, 0.02, and <0.01, respectively). The incidence of severe adverse events, however, was comparable in the 2 groups: 20% in group RS and 19.2% in group S. The median progression-free survival (PFS) of EHS or MVI, PFS of whole lesions, and overall survival were longer in group RS (13.5, 10.6, and 31.2 months, respectively) than in group S (3.3, 3.5, and 12.1 months, respectively) (p<0.01 for all). Conclusion Sorafenib in combination with radiotherapy is a feasible and tolerable treatment option for advanced HCC.