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Introduction: Although many treatment options are available for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class A, those for patients with CP class B remain limited. We aimed to assess the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil and cisplatin in patients with advanced HCC and CP class B. Methods: Sixty patients who received HAIC with 5-fluorouracil and cisplatin at Kurume Chuo Hospital between April 2012 and March 2021 were recruited. Cisplatin (30 mg administered over 2 h) and 5-fluorouracil (1,250 mg, 72-h constant infusion) were administered to the tumor-feeding artery every 2 weeks. The primary endpoint was overall survival (OS), while the secondary endpoints were progression-free survival and adverse effects. Results: Among the 60 patients, CP class A and class B were noted in 30 patients each. OS did not significantly differ between the two classes. After 4 weeks of HAIC with 5-fluorouracil and cisplatin, 12 patients in the class B group exhibited improved CP scores (CPSs) relative to those at the start of treatment. There was a significant difference in OS between patients whose CPSs had improved and those whose scores remained unchanged or had worsened. Conclusions: HAIC using 5-fluorouracil and cisplatin is effective and safe for patients with CP class B, and improvements in CPSs after 4 weeks of this therapy may represent a predictive marker of treatment efficacy regardless of pretreatment CPS in patients with CP class B.

Background and Aims Sequential therapy with molecular‐targeted agents (MTAs) is considered effective for unresectable hepatocellular carcinoma (HCC) patients. This study purposed to evaluate the efficacy of sequential therapy with sorafenib (SORA) as a first‐line therapy and to investigate the therapeutic impact of SORA in nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steato hepatitis (NASH)‐related HCC. Methods We evaluated 504 HCC patients treated with SORA (Study‐1). The times of administration for sorafenib from 2009 to 2015, 2016 to 2017, and 2018 and later were defined as the early‐, mid‐, and late‐term periods, respectively. Among them, 180 HCC patients treated with SORA in addition to MTAs in the mid‐ and late‐term periods were divided into groups based on disease etiology (NAFLD or NASH [n = 37] and viral or alcohol [n = 143]), and outcomes were compared after inverse probability weighting (IPW) (Study‐2). Results Overall survival (OS) of HCC patients who received sequential MTA therapy after first‐line SORA was significantly longer. The median survival times (MST) were 12.6 versus 17.6 versus 17.4 months in the early‐term group, mid‐term group, and the later‐time group (early vs. mid, p = 0.014, early vs. later. p = 0.045), respectively. (Study‐1). In Study‐2, there was no significant differences in OS between the Virus/alcohol group and the NAFLD/NASH group in patients who received sequential therapy (MST was 23.4 and 27.0 months p = 0.173, respectively). The NAFLD or NASH, female sex, albumin‐bilirubin (ALBI) grade 2b, and major Vp (Vp3/Vp4) were significant factors for OS treated with SORA. Conclusions Sequential therapy with SORA as the first‐line treatment improved the prognosis of unresectable HCC patients and was effective regardless of HCC etiology., Sequential therapy with SORA as the first‐line treatment prolonged the prognosis of unresectable HCC patients and was effective regardless of HCC etiology.

This study aimed to evaluate the correlation between adverse events (AEs) and overall survival (OS) in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab (atezo/beva). This was a multicenter study in which 130 patients were enrolled. Hypertension and skin disorders had a significant correlation with longer survival (median survival time (MST): not reached vs. 14.3 months and not reached vs. 14.8 months, p = 0.001 and p = 0.047, respectively). In contrast, liver injuries were significantly correlated with shorter survival (MST: 14.7 months vs. not reached, p = 0.036), and the median development time was 21 days. In a logistic regression analysis, fatigue ≥ grade 2, liver injury ≥ grade 3, and modified albumin–bilirubin grade 2b were identified as independent factors for discontinuation due to AEs. The OS in the no discontinuation due to AE group was significantly longer than that in the discontinuation due to AEs group (MST not reached vs. 11.2 months, p = 0.001). We concluded that the development of liver injury was a negative factor for OS and that we should be vigilant in monitoring AE during atezo/beva treatments.

Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, as the resectability rate is low due to its diagnosis at a late/advanced stage. Moreover, most patients with resected ICC eventually relapse. Hepatic arterial infusion chemotherapy (HAIC) has been indicated only by a few reports to be effective in patients with advanced ICC; thus, its efficacy for these patients remains unclear. This study aimed to evaluate the efficacy of HAIC using gemcitabine, cisplatin, and 5-fluorouracil in patients with advanced ICC. A total of 18 patients who underwent HAIC were retrospectively investigated. The patients received gemcitabine, cisplatin, and 5-fluorouracil through one artery. In patients who received gemcitabine plus cisplatin (n = 10), the response and disease control rates were 0% and 80.0%, respectively; the median overall survival (OS) and progression-free survival (PFS) after treatment initiation were 6.3 and 3.7 months, respectively. In patients who never received chemotherapy (n = 8), the response and disease control rates were 37.5% and 75%, respectively; the median OS and PFS were 20.6 and 8.1 months, respectively. Moreover, we compared the patients who received HAIC using gemcitabine, cisplatin, and 5-fluorouracil to patients whose tumors were refractory to systemic gemcitabine and cisplatin therapy. The OS of the patients who received HAIC was better than that of the patients who received standard chemotherapy cohort since the gemcitabine plus cisplatin combination therapy-refractory response and disease onset (P = 0.045, 0.006). HAIC using gemcitabine, cisplatin, and 5-fluorouracil may be effective as a therapeutic option for patients with advanced ICC.

PURPOSE An indwelling arterial access system via the brachial artery, System-i, has been previously reported. We have modified the technique for the femoral artery approach. This study aimed to evaluate the feasibility and safety of the modified System-i for patients with malignant liver tumors. MATERIALS AND METHODS The modified System-i is an indwelling catheter that provides vascular access for inserting a microcatheter without repeated punctures to the femoral artery. Between 2018 and 2020, the system was implanted for 50 patients with malignant liver tumors. We used the system for patients with difficulty in inserting the conventional indwelling catheter system. To place the system, a side-holed catheter was implanted in the femoral artery, and the tip of the catheter was placed in the superficial femoral artery through the contralateral iliac artery. Using this system, transcatheter arterial chemoembolization or hepatic arterial infusion chemotherapy was performed. A shaped high-flow microcatheter and a non-tapered microcatheter were used with the system. The technical aspects and outcomes of the system were also assessed. RESULTS Implantation of the system was successful in all patients. The median implantation time was 40 min. The main reason for implantation was obstruction or stenosis of the hepatic artery. Among the 50 patients, 11 (22%) showed complications, of which four had major complications/class C based on the SIR criteria. CONCLUSION The modified System-i is a safe system that can be a feasible repeated interventional radiological treatment via the femoral approach. We need to evaluate the efficacy of this system in the treatment of advanced cancers in the future. The modified System-i is a novel indwelling catheter system that allows vascular access to perform intermittent transarterial therapy, such as transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy via the femoral approach. In this study, we report the technical details and safety of the system.

BACKROUND: Not all patients with hepatocellular carcinoma (HCC) benefit from treatment with molecular targeted agents such as sorafenib. We investigated whether New-FP (fine-powder cisplatin and 5-fluorouracil), a hepatic arterial infusion chemotherapy regimen, is more favorable than sorafenib as an initial treatment for locally progressed HCC. METHODS: To avoid selection bias, we corrected the data from different facilities that did or did not perform New-FP therapy. In total, 1709 consecutive patients with HCC initially treated with New-FP or sorafenib, 1624 (New-FP, n = 644, sorafenib n = 980) were assessed. After propensity score matching (PSM), overall survival (OS) and prognostic factors were assessed (n = 344 each). Additionally, the patients were categorized into four groups: cohort-1 [(without macrovascular invasion (MVI) and extrahepatic spread (EHS)], cohort-2 (with MVI), cohort-3 (with EHS), and cohort-4 (with MVI and EHS) to clarify the efficacy of each treatment. RESULTS: New-FP prolonged OS than sorafenib after PSM (New-FP, 12 months, sorafenib, 7.9 months, p &lt, 0.001). Sorafenib treatment, and severe MVI and EHS were poor prognostic factors. In the subgroup analyses, the OS was significantly longer the New-FP group in cohort-2. CONCLUSIONS: Local treatment using New-FP is a potentially superior initial treatment compared with sorafenib as a multidisciplinary treatment in locally progressed HCC without EHS.

BACKGROUND AND AIMS Advanced hepatic fibrosis can occur in patients with various diseases, including diabetes mellitus and hypertension. We aimed to investigate the prevalence and risk factors of advanced hepatic fibrosis in patients with various internal diseases. PATIENTS AND METHODS We performed a community-based survey in which 1012 patients were enrolled (mean age, 63.1 ± 10.8 years; female/male, 505/507). Hepatic fibrosis was evaluated by Fib-4 index and patients were classified into high and low Fib-4 groups. Independent factors for the high Fib-4 group were analyzed using logistic regression and decision tree analysis. RESULTS A high prevalence of high Fib-4 index was observed in patients with cardiovascular diseases; 37.1% of patients with hypertension belonged to the high Fib-4 group. Independent factors associated with the high Fib-4 group were BMI (OR 0.95, 95%CI 0.918-0.989, P

Advanced hepatic fibrosis can occur in patients with various diseases, including diabetes mellitus and hypertension. We aimed to investigate the prevalence and risk factors of advanced hepatic fibrosis in patients with various internal diseases.We performed a community-based survey in which 1012 patients were enrolled (mean age, 63.1 ± 10.8 years; female/male, 505/507). Hepatic fibrosis was evaluated by Fib-4 index and patients were classified into high and low Fib-4 groups. Independent factors for the high Fib-4 group were analyzed using logistic regression and decision tree analysis.A high prevalence of high Fib-4 index was observed in patients with cardiovascular diseases; 37.1% of patients with hypertension belonged to the high Fib-4 group. Independent factors associated with the high Fib-4 group were BMI (OR 0.95, 95%CI 0.918-0.989, P 0.01), male sex (OR 1.35, 95%CI 1.03-1.78, P 0.05), and hypertension (OR 1.41, 95%CI 1.03-1.92, P 0.05). In patients with hypertension, a decision tree algorithm revealed three profiles for Fib-4 index: 1) creatinine level 0.76 mg/dL (high Fib-4; 30.0%), 2) creatinine level ≥ 0.76 mg/dL without sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment (high Fib-4; 48.2%), and 3) creatinine level ≥ 0.76 mg/dL with SGLT2i treatment (high Fib-4; 23.5%).A high prevalence of advanced hepatic fibrosis was observed in patients with hypertension. Hypertension was an independent risk factor, and creatinine level and SGLT2i were divergence variables for advanced hepatic fibrosis. Thus, hypertension with chronic kidney injury may exacerbate hepatic fibrosis, while SGLT2i treatment may ameliorate hepatic fibrosis.

Purpose This paper describes the technical details of the new indwelling catheter system, which we refer to as System-i, and provides an overview of our experience with this system at our institution. Materials and methods The system is implanted via the left brachial artery. The feeding artery of the tumor is catheterized at each treatment, and the system can be used for multiple treatments via more than one feeding artery. Between January 2004 and January 2013, System-i was used to administer 398 treatments in 30 patients with hepatocellular carcinoma (HCC). The technical aspects and outcomes of treatment procedures were evaluated. Results Implantation was successful in all cases. Systemi was used for a median number of 11 treatments per patient over a median period of 5.7 months, and 71.6 % of all treatments were administered on an outpatient basis. Conclusion System-i provides an effective and safe method for selective catheterization of feeding arteries for administration of transcatheter arterial chemoembolization or infusion in patients with HCC. Treatment regimens can be individualized without limiting the number of treatments or treatment locations, and patients can be treated on an outpatient basis.

症例は41歳，女性．５年前より右鼠径部に腫瘤を自覚，平成18年に入り腫瘤が圧痛を伴い周期的に大きくなるといった症状が加わったため当院外来を受診となった．触診にて右鼠径部に３cm大・弾性硬な腫瘤を触知，超音波・骨盤部CTよりNuck管水腫，粘液腫等を疑いインフォームドコンセントの上，診断・治療目的に手術を施行した．腫瘤は子宮円索末梢側に存在したため，子宮円索を含めて腫瘤を切除した．病理組織検査にて組織内に子宮内膜類似組織が混在しており，子宮内膜症と診断された．本症は外性子宮内膜症のうち約0.8％と比較的稀な疾患であり診断に難渋することが多いが，充分な病歴の聴取により症状と月経周期との関係を把握することが診断のポイントであると考えられる．鼠径部の腫瘤を主訴に来院した症例の診察にあたっては本症を鑑別診断の一つにあげ慎重な病歴の聴取を行う必要があると思われた．

We describe a 48-year-old man with nodular intrahepatic lesions accompanied by communication between the inferior vena cava and portal systems as well as absence of intrahepatic portal veins. After infection with malaria in childhood, end-to-side portacaval shunting had been performed to treat upper gastrointestinal bleeding at the age of 15 years. A biopsy specimen obtained under ultrasonographic guidance showed hyperplastic nodules suggestive of focal nodular hyperplasia. The estradiol concentration in the blood was elevated (55 pg/ml). This case suggests that portacaval shunting may be associated with hyperplastic liver nodules through hyperestrogenemia and abnormal hepatic hemodynamics.

Background/Aims: This study aimed to evaluate the usefulness of 18F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) and PET plus computed tomography (CT) fusion images for the detection of extrahepatic metastases of hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (combined HCC/CC). Methods: Twenty-one patients with HCC and combined HCC/CC were enrolled in the study from December 2004 to February 2005. In all patients, PET and CT of the chest to pelvis region were performed. The sensitivity of PET plus CT fusion images was compared with the sensitivity of PET, CT, and bone scintigraphy. Results: In 14 patients, a total of 58 extrahepatic metastases were diagnosed. The detection rate of PET plus CT fusion images, PET, CT, and bone scintigraphy was 98.2% (57 of 58 metastases), 89.6% (52 of 58 metastases), 91.2% (52 of 57 metastases), and 68.7% (11 of 16 bone metastases), respectively. No extrahepatic metastases were detected in the other seven patients. The detection rate of PET was 10/18 (55.6%) for intrahepatic lesions of HCC and combined HCC/CC. Conclusions: The fusion of PET plus CT images is useful in detecting extrahepatic metastases in HCC and combined HCC/CC patients.

Loss of appetite is frequently seen and is a main factor affecting quality of life (QOL) in patients with advanced cancer. The etiology for loss of appetite in patients with cancer is multifactorial. The sensory properties of food are factors regulating appetite. Changes in taste, smell and texture of foods influence food intake. The appearance of the food is also a notable factor in sensory-specific satiety. We described a 46-year-old Japanese woman with multiple metastatic liver tumors. Although there was no obvious factor for loss of appetite, she suffered from a loss of appetite and subsequent malnutrition. In order to improve the appearance of food, we reduced the diet to 1,000 kcal/day from 1,500 kcal/day. On the new diet, the patient's appetite significantly increased and patient's nutritional status was improved. Eating whole diet was an important achievement and increased in mental aspects of QOL. Arrangement for the appearance of food may be a simple and nontoxic therapeutic strategy for patients with cancer suffering a loss of appetite.

症例は52歳の女性. 主訴は食後の腹満感, 嘔吐と体重減少. 近医の上部消化管造影X線検査で横隔膜ヘルニアと診断され, 当院を紹介され来院した. 当院の検査では, 食道裂孔ヘルニアで胃前庭部と十二指腸球部がヘルニア内に脱出嵌頓して通過障害を来していることが診断された. 内視鏡的整復が困難と判断され開腹手術を行い, 嵌頓した胃前庭部と十二指腸球部を還納後, ヘルニア門を縫合閉鎖して手術を終了した. 術後の上部消化管造影X線検査では正常な解剖学的位置関係に復しており, 通過も良好であった. 食道裂孔ヘルニアの定義では, 胃の漿膜を含む全層が胸縦隔内へ脱出する状態をいい, 胃以外の腹腔内臓器が脱出することは極めてまれとされている. 文献検索では, 十二指腸球部を内容とした食道裂孔ヘルニアの報告は4例のみで自験例は5 例目であり, 極めてまれであると考えられたので報告した.

We report a rare adult case of gallbladder agenesis with no other biliary tract abnormality. The patient was a 29-year-old man with pain in the right upper-quadrant of the abdomen, and vomiting. The gallbladder was not visualized by ultrasonography, computed tomography, or endoscopic retrograde cholangiography. The common bile duct was slightly dilated. No other abnormalities, including anomalous choledochopancreatic duct junction, were found. Based on these imaging findings and the patient's right hypochondrial pain, there was a high index of suspicion of chronic cholecystitis caused by incarcerated gallstones in the neck of the gallbladder. At operation, we carefully observed the gallbladder fossa, using laparoscopy, and found gallbladder to be absent. Although the operation involved only observation via a laparoscope, the patient has since remained well and asymptomatic. It is difficult to make a correct diagnosis of gallbladder agenesis preoperatively. We believe that, if the gallbladder is not visualized by imaging techniques, it may be better to perform laparoscopy for observation before performing laparotomy, in order to reduce surgical stress.

患者は72歳の女性. 55歳の時に交通事故で骨盤を骨折. 3年前よりときどき右下腹部痛, 下痢がみられ, 当院を受診. 触診では右下腹部から側腹部にかけて圧痛を認めたが, 腹膜刺激症状はなく, 腫瘤も触知しなかった. その後も症状が続くため平成10年に注腸造影X線検査 (以下, 注腸Xp), Computed tomography (以下, CT) を施行し, 上行結腸の腹腔内からの脱出を認めた. 腰ヘルニアを疑い, 手術を行うも胸腰筋膜のレベルで, 外腹斜筋の中に腸骨稜を下端とした直径4cmの欠損部があり, 上腰三角, 下腰三角は脆弱でないため, 腰ヘルニアではなく, 17年前の外傷による腹壁ヘルニアと診断, 周辺組織を縫合することで欠損部を閉鎖した. 術後は良好に経過中である. 外傷性腹壁ヘルニアは鈍的, 鋭的損傷, または介達外力による損傷の結果生じるヘルニアである. 受傷後まもなく発生する場合と遅発性に発生する場合があるが, 後者はその中でもまれといわれている. 自験例では注腸Xp, CTがヘルニアの存在診断に有用であると考えられた.

We report three non-typical cases of renal angiomyolipoma including clinical features, imaging examinations (with ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography) and histological findings. Microaneurysms observed by angiography were common to the three cases and were considered to be an important finding in the diagnosis of renal angiomyolipoma. Moreover, the short tau inversion recovery (STIR) method of MRI, which suppresses photon signals of fat, was considered to be useful for the diagnosis. Case 1 was accompanied by spontaneous rupture, Case 2 was difficult to diagnose because of little fat tissue and Case 3 revealed a very small tumor.

We performed a liver scintigraphy using technetium-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin ( 99m Tc-GSA), which images the functional liver mass through its binding to the specific receptor asialoglycoprotein receptor in patients with severe alcoholic hepatitis. Receptor index (LHL 15) was significantly lower in patients with alcoholic hepatitis, compared with controls with normal liver. Difference in the isotope uptake patterns between liver and heart varied according to the severity of liver disease, and made it possible to categorize 5 grades. Grading score could discriminate between the eventual outcome of the patients. Furthermore, single photon emission computed tomography showed the variable uptake patterns in the hepatic lobule, wherein there were no evident findings in macroscopic view at autopsy. The results of this study show the usefulness of 99m Tc-GSA scintigraphy in the evaluation and prognosis of alcoholic hepatitis.

Magnetic resonance imaging (MRI) and computed tomography (CT) were performed in four patients with thorotrastosis. On CT scan, Thorotrast (thorium oxide) deposition was shown as high-density areas in the liver and spleen and the abdominal lymph nodes. These deposits were not found on MRIs. Splenic volume was significantly small due to atrophy. The contrast-noise ratio in the spleen on T1-weighted images was significantly lower. Thorotrast deposition does not affect MRI appearance; therefore it may be useful for the early detection of malignant tumors as a complication of thorotrastosis.

A 47-year-old man with primary amyloidosis was admitted with abdominal pain. A new radionuclide liver imaging technique using Technetium-99 m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was performed and the serum hyaluronate concentration was measured. Although ordinary laboratory tests revealed only slight abnormalities, the uptake of the radiolabelled ligand for hepatocyte asialo-glycoprotein receptors was dereased, and marked hepatomegaly was revealed. Furthermore, the serum hyaluronate level was elevated. Histological examination of a hepatic needle biopsy specimen revealed a marked deposition of amyloid in the hepatic perisinusoidal spaces. These results indicate, that this new radionuclide liver imaging technique (using Technetium-99 m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin) and the measurement of serum hyaluronate may be useful supplementary tools for identifying amyloid deposition in the hepatic perisinusoidal spaces in patients with amyloidosis.

The process of receptor-mediated endocytosis is common to a variety of species and cell types. One of the best characterized receptor-ligand systems is the hepatocyte receptor for asialoglycoproteins. We investigated the morphological features of the uptake and intracellular transport of gold-conjugated asialofetuin in isolated rat hepatocyte couplets. We assessed the effects of colchicine, lumicolchicine, cytochalasin B, and chloroquine on the uptake and intracellular transport of asialoglycoproteins. Isolated rat hepatocyte couplets were incubated with gold-conjugated asialofetuin, and transmission electron micrographs of these cells were analyzed to determine the density and distribution of gold particles in the peripheral and pericanalicular areas. Results were analyzed morphometrically. Colchicine significantly inhibited the uptake and intracellular transport of asialoglycoproteins, but did not affect membrane fusion of endocytic compartments in the peripheral area. Lumicolchicine and cytochalasin B had minimal effects on these processes. Chloroquine inhibited the uptake of asialoglycoproteins, but did not affect the intracellular transport of asialoglycoproteins. Results suggest that the microtubule is essential for intracellular movement of endocytosed asialoglycoproteins and receptor recycling, and that endocytic structures in the peripheral regions can fuse in the absence of intact microtubules. We also found that uptake and intracellular transport of asialoglycoproteins were independent of the microfilaments, and the pH gradient in endocytic compartments was important in receptor-mediated endocytosis of asialoglycoproteins.

To assess whether the hepatocyte asialoglycoprotein receptors are affected in patients with autoimmune hepatitis, the function of the hepatocyte asialoglycoprotein receptor was investigated in patients with autoimmune hepatitis or chronic hepatitis C. A new radionuclide liver imaging technique, Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was applied to evaluate the function of the receptor. A Receptor Index (LHL 15) was calculated by dividing the radioactivity of the liver region-of-interest (ROI) by that of the liver plus heart ROI 15 min after radiolabeled ligand injection. Serum albumin, prothrombin time, hepaplastin test and plasma retention rate of indocyanine green at 15 min were not significantly different between patients in the autoimmune hepatitis group and chronic hepatitis C group. In addition, the Receptor Index of patients with autoimmune hepatitis, in whom the asialoglycoprotein receptor is a candidate target antigen for autoimmune response, was similar to that of patients with chronic hepatitis C. These results indicate that the hepatocyte receptor for asialoglycoproteins is not affected in patients with autoimmune hepatitis.

Myelolipoma of the adrenal gland is a non-functioning benign tumor. In this paper 2 cases of this relatively rare disease are described. Case 1: A 36-year-old man was admitted to the hospital because of an abdominal tumor and pain. The abdominal tumor was diagnosed as lipoma originating in the bilateral adrenal glands. Case 2: A 48-year-old man had been suffering from hypertension and diabetes meritus. Abdominal ultrasonography indicated an unexpected tumor shadow in the right adrenal gland. The pathological diagnosis of the resected tumors was myelolipoma originating in the adrenal gland. Seventy-four cases of this tumor, including these 2 cases, have been reported in the Japanese literature. An average age of this patient group was 51.8 years old. The tumor is slightly predominant in men and frequently found on the right lateral gland. Averaged weight of the tumor was 405.6g. Case 1 had the heaviest tumor, 2560g. In diagnosis of this tumor, CT, ultrasonography, and MRI are useful. In the treatment, tumors which are accompanied with some symptoms such as pain, or are too large probably to cause bleeding should be subjected to operation, however, another tumors which have no pain and small in size should be followed strictly.

This paper reports a case with an undifferentiated carcinoma of the esophagus which primarily developed symptoms due to metastatic lesions. The case was a 59-year-old woman with a primary manifestation of an abdominal mass and with subsequent dysphagia. A protruding lesion with ulceration was found at the lower third of the thoracic esophagus by endoscopic examination and was histologically proved to be an undifferentiated carcinoma by biopsy. The abdominal mass was initially thought to be due to metastasis to an abdominal lymph node based on the diagnosis image finding at admission, but it was consequently found by autopsy to be a metastatic tumor in the liver. Therefore, undifferentiated carcinoma of the esophagus should be take into account for differential diagnosis of an abdominal mass.

A case of spontaneous rupture of the esophagus with a gastric cancer, which was successfully cured by conservative therapy, is experienced. A 65-year-old man was seen at the hospital because of sudden onset of hematemesis. By emergency CT and endoscopic examination, an advanced gastric cancer and hydrothorax were found. An emergency operation was performed. Esophagography after partial gastrectomy revealed a leakage in the lower portion of the esophagus. A diagnosis of spontaneous rupture of the esophagus with its resultant pyothorax was made. Because of his poor pyothorax condition after the operation, he was treated conservatively and cured.As a general rule, spontaneous rupture of the esophagus requires early diagnosis and emergency surgical management. However for patients in poor general condition like this case, conservative therapy should be selected.

A case of colon cancer in pregnancy is reported. A 37-year-old pregnant woman visited a nearby hospital because of diarrhoea and bloody stool, which developed in the later period of pregnancy. She was diagnosed as gestosis and underwent cesarean section. After the surgery, however, bloody stool still continued and she was referred to the hospital. As a result of various examinations, an advanced colon cancer was found in the ascending colon and right hemicolectomy was performed. Histological diagnosis was well-differentiated adenocarcinoma, pm, ly1, v0, n1, ow(-), aw(-), absolute curative operation.Colorectal cancer in pregnancy is rare. It is said that one or two among 100, 000 pregnant women may have the disease. An association of colonic cancer is particularly rare, and only 36 cases can be seen in the Japanese literature. This case was the 37th one. In view of this possible association in pregnant women, we would emphasize the importance of early detection and early diagnosis by appropriate examinations.

We report a case of insulinoma associated with early gastric cancer, together with reviwe of the literature. In a 65-year-old man complaining of abnormal behavior at empty stomach, insulinoma was suspected because his conditions satisfied the three characteristics proposed by Whipple but no definite findings indicating insulinoma was shown by another examinations. Moreover, PTPC offered only a suspicion of insulinoma at the caput pancreatis, and imaging diagnostic methods failed to vivalize it. From these findings, a possibility of ectopic insulinoma was considered, and upper intestinal series revealed an early gastric cancer. On laparotomy, insulinoma was confirmed at the caput pancreatis by ultrasonography perioperatively. We did distal gastrectomy (R2) and enucleation of insulinoma. The gastric cancer had no lymphnode matastasis and was of early one retaining within the mucous membranes. Postoperative course was uneventful.

Glucose intolerance frequently is found in hepatocellular carcinoma (HCC) patients with hepatitis C virus (HCV) infection; however, the significance of glucose intolerance remains unclear. In addition, SH2 domain-containing inositol phosphatase (SHIP) 2 is a negative regulator of intracellular insulin signaling; however, changes in SHIP2 expression have not been investigated in HCC. To assess the significance of glucose intolerance, we analyzed 118 HCC patients with HCV infection. Twenty HCC specimens were used for immunoblotting and immunostaining for SHIP2. Patients were classified into two groups: a glucose intolerance group (n=39) and a normal glucose tolerance group (n=79). There was no significant difference in the disease-free survival (P=0.838) or long-term survival (P=0.091) between the groups. However, for males, the cumulative survival rate was significantly lower in the glucose intolerance group (n=22) than that in the normal glucose tolerance group (n=52) (P=0.036). In multivariate analysis, Child-Pugh class (P=0.0003) and glucose intolerance (P=0.036) were identified as statistically significant and independent prognostic factors in males. SHIP2 expression level decreased in HCC compared to that in nontumor tissues. In conclusion, this study is the first to demonstrate the significance of glucose intolerance in prognosis of male HCC patients and down-regulation of SHIP2 expression in HCC.

OBJECTIVE. The purpose of our study was to evaluate retrospectively the usefulness and complications associated with a temporary indwelling catheter system through the brachial artery for patients with liver tumors.CONCLUSION. The temporary indwelling catheter system via the left brachial artery can be used not only for CO2-enhanced sonographically guided aspiration biopsy, radiofrequency ablation, and percutaneous ethanol injection, but also for short-term hepatic arterial infusion chemotherapy and transcatheter arterial chemoembolization.

Signet-ring cell carcinoma (SRC) of the stomach exhibits diffuse growth and invasion without forming ducts. Destruction of the surrounding basal membrane and angiogenesis appear to be required for SRC to exhibit marked invasion and growth. We recently reported that heparanase (HPA) and cyclooxygenase-2 (COX-2) were strongly correlated with microvessel density, and that COX-2 expression is up-regulated by HPA in esophageal cancer. In this study, we examined the relationship between HPA expression and that of COX-2 in SRC of the stomach. We examined HPA and COX-2 expression in 3 cell lines derived from SRC of the stomach and in 50 SRC lesions of stomach by immunohistochemistry (IHC), in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR). We also examined the relationships among HPA expression, COX-2 expression, and the clinicopathologic features of SRC, mean age, sex, invasion depth, regional lymph node metastasis, lymphatic invasion, and venous blood vessel invasion. Of the 3 cell lines, 2 exhibited both HPA and COX-2 mRNA expression on RT-PCR. Of the 3 cell lines, 1 exhibited only HPA mRNA expression on RT-PCR. Heparanase expression was confirmed in 23 (46%) of 50 tumor samples by IHC. COX-2 expression was confirmed in 25 (50%) of the 50 tumor samples by IHC. In situ hybridization revealed messenger RNA expression in the same area as in that revealed by IHC. A close correlation was noted between HPA and COX-2 expressions (P < .0001). The present study thus elucidated the biologic features of SRC of the stomach related to growth and angiogenesis.

Exacerbation of liver damage during transhepatic arterial infusion chemotherapy (THAIC) is a critical complication in patients with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). We previously reported that HBe antigen positivity was the associating factor for the exacerbation of liver damage. In the present study, we investigated the effect of lamivudine administration for exacerbation of liver damage in such patients.Seventeen patients with HBV-related hepatocellular carcinoma who received THAIC were reviewed. Eight of these patients received lamivudine administration. Nine patients did not receive lamivudine administration. All patients were HBe antigen positive. Liver function tests, liver enzymes, HBV-DNA levels, HBe antigen, HBe antibody, and mutation in the precore and core-promoter regions of HBV DNA were evaluated.In the lamivudine-treated group, HBV-DNA levels were significantly reduced and did not increase throughout chemotherapy. Lamivudine did not induce any changes in precore or core-promoter regions. Although levels of alanine aminotransferase (ALT), asparate aminotransferase (AST), total bilirubin, and prothrombin time (PT) in the lamivudine-treated group did not change, levels of ALT, AST and total bilirubin increased, and PT were prolonged in the untreated group by chemotherapy. No patients receiving lamivudine administration showed exacerbation of liver damage. Exacerbation of liver damage was detected in six patients without lamivudine administration. Of these, three patients died of progressive liver failure due to reactivation of HBV.These results indicate that prophylactic lamivudine administration reduces HBV-DNA levels and prevents exacerbation of liver damage throughout the period of chemotherapy in HBe antigen positive patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Flare-up of hepatitis due to the reactivation of hepatitis B virus (HBV) is a well-known complication in patients with malignant disease who receive chemotherapy. Despite the widespread use of chemotherapy for patients with HBV-related hepatocellular carcinoma (HCC), there is little corresponding data on exacerbation of liver damage in these patients. In the present study, we investigated the associating factors in exacerbation of liver damage in patients with HBV-related HCC who were undergoing trans-hepatic arterial infusion chemotherapy (THAIC). PATIENTS AND METHODS: Thirty-three patients who received THAIC for HCC were investigated. All patients were hepatitis B surface antigen positive. Hepatitis e antigen and antibody were generally tested at baseline and within 1 month of final chemotherapy. Serum alanine aminotransferase, asparate aminotransferase, albumin, total bilirubin, and prothrombin time were estimated once a week or every 2 weeks. HBV-DNA levels were measured at baseline and once a month. Mutation in the regions of precore and core promoter in HBV DNA was generally estimated at baseline and within 1 month of final chemotherapy. RESULTS: Eight patients with hepatitis Be antigen positive and hepatitis Be antibody negative at baseline were found to have exacerbation of liver damage during or after chemotherapy. Of these, three patients died of progressive liver failure. There was no association between exacerbation of liver damage and age, sex, hepatic reserve function, HBV-DNA levels, precore and core promoter sequencing, therapeutic regimen, or tumor stage. The only associating factor was HBeAg positivity. CONCLUSIONS: These results suggest that hepatitis B e antigen positivity is a significant associating factor in exacerbation of liver damage during or after chemotherapy in patients with HBV-related HCC.

Radiofrequency ablation (RFA) is an effective procedure for localized hepatocellular carcinoma. Contrast-enhanced CT depicts the ablated area as a hypoattenuated area without hepatic blood flow; however, light microscopy does not show obvious necrosis in the ablated area. We evaluated liver tissue changes after RFA by light microscopy and electron microscopy. The normal livers of three anesthetized pigs were coagulated using RFA after laparotomy. The liver was examined immediately, and 1 week after operation by light and electron microscopy. After RFA, the liver parenchyma surrounding the needle electrode was brown in color and surrounded by a red marginal zone separate from the normal liver parenchyma. Hematoxylin-eosin staining of the central area did not show cell necrosis, and the structures of liver sinusoids, liver cell cord and the nuclei of hepatocytes were preserved. However, electron microscopic examination of tissue immediately after RFA showed destruction of mitochondria of hepatocytes and fixation of sinusoidal cells. One week later, there was a large quantity of debris in the enlarged sinusoids, in addition to irreversible destruction of hepatocyte organelles. RFA of the porcine liver causes hepatocyte damage. This damage was not evident by light microscopy but clearly identified by electron microscopy.

We report a case of appendicitis caused by amebiasis in a 45-year-old Japanese man. He presented to our hospital with bloody stools in June 1998. Sigmoidoscopy disclosed erosion, and a biopsy of the erosion showed colitis caused by Entamoeba histolytica infection. Four months later, he was admitted to our hospital with a small elastic mass and severe pain in the lower quadrant of the abdomen, which was diagnosed as acute appendicitis. He underwent appendectomy. Histopathological examination revealed numerous E. histolytica trophozoites, and we diagnosed acute appendicitis caused by E. histolytica. The patient has been free of symptoms, colonoscopy has revealed no erosion, and biopsy has revealed no E. histolytica for 12 months after the operation.

To elucidate the risk factors for developing hepatocellular carcinoma (HCC) during the follow-up of patients with liver cirrhosis (LC), outpatients with LC were examined periodically by means of serum biochemical assessments, ultrasonography, and computed tomography. Risk factors for HCC were statistically analyzed. We also examined an efficacy of Lens culinaris agglutinin A-reactive profiles of alpha-fetoprotein (AFP-L3%) and des-gamma-carboxy prothrombin (DCP) value using a highly sensitive DCP determination kit (ED036) for the early recognition of HCC. The AFP-L3% and the ED036 value were retrospectively determined with stored serum samples. HCC was diagnosed in 21 of the 78 patients with LC during the follow-up period (mean follow-up period: 42 months). The estimated cumulative incidence of HCC was 25% with 3 years and 48% with 5 years. The most significant risk factor for the development of HCC in LC patients was found to be the mean serum AFP concentration from the year before the HCC detection (p=0.02). At the time of the recognition of HCC, the positive rates of the tumor markers were: serum AFP concentration 14%, serum DCP value 5%, AFP-L3% was 33%, and that of ED036 43%. The positive rate in collaborative use of AFP-L3% and ED036 was 67%. The simultaneous determination of the AFP-L3% and the ED036 value was shown to be effective for the early detection of HCC.

We investigated the effect of hepatic artery infusion (HAI) chemotherapy on advanced hepatocellular carcinoma. Ten milligrams per hour of cisplatin for 1 h and subsequently 250mg/h for 5h of 5-fluorouracil were administered using a subcutaneously implanted vascular access device (an injection port) for 5 consecutive days followed by 2 days rest. One course consisted of repetition of the above dosage regimen for 4 weeks. We treated 77 patients with advanced hepatocellular carcinoma (HCC), excluding nodular-type tumors indicated for chemoembolization, percutaneous ethanol injection therapy, or hepatic resection. Vascular invasion was seen in 28 patients and distant metastasis was seen in 7 patients. Of patients with advanced HCC, 77% were at tumor stage IV. Ten patients (13%) had a complete response, 25 (32%) had a partial response, 30 (39%) exhibited no change, and 12 (16%) had progressive disease. The response rate was thus 46%. Estimated 1-year, 2-year, and 3-year survival by the Kaplan-Meier method in 77 patients was 56%, 28%, and 19%, respectively. According to a multivariate analysis, the effects of initial therapy (P > .0001) and the Child-Pugh grade (P = .0012) were significant prognostic factors. A survival benefit was noted in patients with portal vein invasion (1-year survival rate: 43%, 2- year survival rate: 24%) when compared with reported results, and HAI was considered to be the first choice for unresectable cases. Adverse reactions of patients were tolerable and included transient nausea, loss of appetite, and mild thrombocytopenia. In conclusion, HAI chemotherapy with the regimen described achieved favorable results, and is useful in treating patients with advanced HCC not indicating chemoembolization, hepatic resection, or ethanol injection therapy.

e14080 Background: At present, systemic chemotherapy is the only established treatment in patients with unresectable colorectal liver metastases (CRLM). The regimen combining irinotecan or oxaliplatin to 5-FU/LV is recommended as a first and second line treatment. However, after failure of oxaliplatin- or irinotecan-based combination chemotherapy, there is no effective regimenremained. This pilot clinical trial explored the feasibility, safety, and efficacy of sequential chemotherapy of hepatic arterial infusion of FOLFOX and FOLFIRI with Intravenous Bevacizumab in unresectable CRLM after systemic chemotherapy failure. Methods: Patients with unresectable CRLM and history of systemic chemotherapy failure were treated with HAI oxaliplatin (35 mg/m2 2 hours: HAI-FOLFOX) or irinotecan (50 mg/m2 2 hours: HAI-FOLFIRI) followed by 5FU (1500mg 46hours) combined with intravenous Bevacizumab (200mg 90min) and LV (200mg 2hours) every 2 weeks until disease progression. Basically, HAI-FOLFOX was applied first, and after disease progression or limiting toxicity, HAI-FOLFIRI followed when the patient was still able to receive treatment. Results: Fourteen consecutive patients (median age 65 years; mean therapeutic term of prior systemic chemotherapy regimens,533 ± 266 days) were included, of whom 11 (79%) had previously received oxaliplatin (n =5), irinotecan (n = 2), or both (n = 4). Patients received a median of 13 cycles of HAI-FOLFOX (range 4–32) and among those, 7 patients sequentially received a median of 22 cycles of HAI-FOLFIRI (range 2–42). There was no technical nonfeasibility to discontinue treatment. The regimen was generally well tolerated; the most common side effects were grade 1 fatigue, anorexia, and/or hypertension. The complete and partial response rate totaled 71.4% in this sequential therapy. Median survival time was 20.1 months. Conclusions: A sequential chemotherapy of hepatic arterial infusion of FOLFOX and FOLFIRI with intravenous bevacizumab is feasible, safe, and shows promising activity in unresectable CRLM after systemic chemotherapy failure.

[Introduction] Detection of sentinel lymph nodes (SN) has been used to predict regional lymph node (LN) metastasis in patients with various types of carcinoma. The technique used to detect SN has focused on using a vital blue dye, a radioactive tracer, or a combination of both. However there are several problems in the current method for SN identification, such as anaphylaxis shock, difficulties of detection, danger of radiation exposure, the limitation of use of radioisotopes, and short shelf life. The aim of this study was to develop new SN identification method using magnetic nanoparticles (MNPs) by MRI. [Methods] 5-week-old, Male Donryu rats were used for establishment of rat SN model and for optimization of MNPs size and amount. 4-week-old, male nude rats (F344/NJcl-rnu/rnu) were used for establishment of metastatic model. Three kinds of MNPs (4 nm (M4), 8 nm (M8), 20 nm (M20)) were synthesized. SN detectability was evaluated by T1-weighted gradient echo MR images after injection of synthesized MNPs or Resovist® in vivo. Signal change of LN induced by MNPs were evaluated T1-weighted MRI slice by two independent researchers. In addition, area (mm2) of susceptibility effect in LN was calculated using ROI tools of MRVision software. All MRI was examined for the receiver operating characteristic (ROC) curves by three individuals whether area of susceptibility was recognizable. ROC displaying sensitivity along with the false-positive rate (1αspecificity) for detecting MNPs by MRI, and the area under the curve with 95% confidence intervals was calculated. The amount of iron in the brachial lymph node (Br) and the axillary lymph node (Ax) was evaluated by inductively coupled plasma optical emission spectrometry (ICP-OES), and evaluated pathologically. MRI was performed weather Br and Ax were distinguishable. To evaluate toxicity of MNPs, exploratory single toxicity study was performed. Over all condition and weight status were observed. [Results] We established an original rat SN model and it revealed that Br is SN and Ax is a higher echelon nodes further downstream from SN. We also established metastatic rat model. M20 was sustained in Br selectively than M4, M8 and Resovist® and appropriate amount was 0.1mg. SN was distinguishable and detectable by MRI using M20 in normal and metastatic rat model. ROC curve analysis revealed that threshold of magnetite amount for MRI detection is 2.3μg/LN with 76.5% sensitivity and 25% specificity, and the area under receiver operating characteristic curve is 0.82 (95% CI, 0.64-1.0). Results of exploratory single toxicity study indicated that the fatal dose was equal to Resovist® and it was tolerable less than medium-low dose (1250 μmol/kg) injection. [Conclusion] We developed the novel SN identification method by MRI with our original 20nm MNPs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 358. doi:1538-7445.AM2012-358

The function of hepatocyte asialoglycoprotein receptors was analyzed in normal subjects, in patients with Wilson's disease and in patients with chronic hepatitis C. A new radionucide liver imaging, using Technetium-99 m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was applied to evaluate the function of the receptor, and a Receptor Index, LHL 15, which was calculated by dividing the radioactivity of the liver region-of-interest (ROT) by that of the liver plus heart ROT at 15 min after the radiolabeled ligand injection, was evaluated. The values were similar between the patients with Wilson's disease and patients with chronic hepatitis C. Hepatocyte receptors for asialoglycoproteins were not affected specifically in patients with Wilson's disease, suggesting that the defect in patients with Wilson's disease involves steps other than receptor-mediated endocytosis of asialoceruloplasmin via asialoglycoprotein receptor.