浅野 岳晴

A 54-year-old man was admitted with obstructive jaundice. Computed tomography showed common bile duct stricture and a tumor around the celiac artery. Repeated endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) as well as a laparotomic biopsy around the celiac artery were diagnostically unsuccessful. Since the bile duct stricture progressed, EUS-FNA and ERCP were performed a third time, finally leading to the diagnosis of diffuse large B-cell lymphoma. The treatment plan and prognosis of obstructive jaundice differ greatly depending on the disease. It is important to conduct careful follow-up and repeated histological examinations with appropriate modifications until a diagnosis is made.

A 66-year-old man underwent a single endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) session and distal pancreatectomy for the pancreatic body adenocarcinoma measuring 12 mm in diameter. At 3 years after surgery, we diagnosed needle tract seeding (NTS) and performed total gastrectomy. NTS can occur with small tumors or after a single session of EUS-FNA.

Immunoreconstitution inflammatory syndrome (IRIS) was reported to occur in 7-13% of AIDS patients on anti-retroviral therapy (ART). IRIS due to Mycobacterium infection is one of the most difficult IRIS types to manage. A male patient in his early 70s was diagnosed with AIDS and treated with an ART. One year after starting ART, abdominal ultrasound was performed for screening and a 4 cm hypoechoic mass was found from the outside of the stomach to the surface of the hepatic lateral segment. Based on various imaging tests, including contrast CT, a malignant tumor, such as malignant lymphoma, was suspected. Then, a percutaneous tumor biopsy was performed. Pathologically, the tumor was recognized as mycobacterial granulomas. Disseminated mycobacterium avium complex can produce granulomas anywhere in the body. The patient was diagnosed with a mycobacterial infection associated with IRIS. When an intra-abdominal mass is found in a patient with HIV, both malignancy and mass formation due to opportunistic infections should be considered differential diseases.

Pruritus is known to be a common complication in hepatitis patients, but the exact frequency and degree are not fully elucidated. Thus, we evaluated pruritus of 450 patients with chronic liver disease at our hospital. Pruritus was observed in 240 (53%) of the patients. Pruritus was significantly associated with males (OR = 1.51, P = 0.038) and patients with alkaline phosphatase (ALP) ≥ 200 U/L (OR = 1.56, P = 0.0495) and was significantly less in HBsAg-positive patients (OR = 0.449, P = 0.004). Seasonally, there was no difference in the frequency of pruritus between summer and winter. Of the 24 refractory pruritus patients treated with nalfurafine, 17 (71%) indicated improvement of itch, which is defined as a decrease in the visual analog scale score ≥ 30 mm. Pruritus was improved by nalfurafine both during daytime and nighttime in the Kawashima's scores evaluation. All patients who received nalfurafine exhibited improved Kawashima's scores ≥ 1 point during the daytime or nighttime. In conclusion, pruritus occurred in > 50% of patients with chronic liver disease, and predictors of pruritus were males and ALP ≥ 200 U/L. Nalfurafine may be useful for pruritus, regardless of whether daytime or nighttime.

Aim: Subepithelial lesions (SELs) are defined as being located under the mucosa. Presently, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is commonly performed to diagnose SELs. With the development of new puncture needles, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB), which allows for the acquisition of large tissue samples, has been proposed. However, studies on EUS-FNB of SELs measuring &lt 20 mm have not yielded satisfactory results. Therefore, we aimed to assess the performance and usefulness of EUS-FNB of SELs measuring less than &lt 20 mm. Methods: The present study included 62 patients who underwent EUS-FNA or EUS-FNB for SELs at our hospital between January 2015 and March 2019. EUS-FNA was performed using fine-needle aspiration needles, and EUS-FNB was performed using fine-needle biopsy needles. These needles, which come in different shapes and diameters, were compared in terms of their usefulness in performing procedures for SELs measuring ≥ 20 mm and those measuring &lt 20 mm. Results: For SELs measuring ≥ 20 mm, the use of needles with a large diameter, such as 19 or 20 G, resulted in significantly improved diagnostic rates. For SELs measuring &lt 20 mm, the use of FNB needles showed significantly improved diagnostic rates, regardless of the size of the puncture needles. Conclusion: Even when SELs are less than 20 mm, they might have malignant potential, and histological diagnosis may be desirable in some cases. EUS-FNB has an advantage over EUS-FNA in the diagnosis of SELs measuring &lt 20 mm.

AIM: This study aimed to evaluate the real-world efficacy and safety of 12-week sofosbuvir/velpatasvir (SOF/VEL) treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus (HCV) infection. METHODS: A total 72 of patients with Child-Pugh (CP) class B or C were enrolled. We evaluated the sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs), and changes in the liver function. RESULTS: All participants had genotype 1 or 2 HCV infection. At baseline, the numbers of patients with CP class B and C were 59 and 13, respectively. The overall SVR12 rate was 95.8% (69/72); 94.9% (56/59) in CP class B and 100% (13/13) in CP class C. The serum albumin level, prothrombin time and ascites were significantly improved (P < 0.01); however, the serum bilirubin level and encephalopathy did not improve. Among patients who achieved SVR12, 75.0% showed an improvement in their CP score, while 5.9% showed a worsening. The presence of large portosystemic shunt (diameter ≥6 mm) and hyperbilirubinemia (≥2.0 mg/dL) were independent factors that interfered with the improvement in the CP score (P < 0.05). The most common AEs were encephalopathy (15.3%) and skin symptoms (7.9%). Two patients discontinued SOF/VEL due to AEs. CONCLUSIONS: Treatment with SOF/VEL for 12 weeks was relatively safe and effective for patients with decompensated cirrhosis. An SVR provided an improvement of the liver function in the majority of patients. However, large portosystemic shunt and hyperbilirubinemia were independent factors that interfered with the improvement in the CP score.

Background: We reported that the pancreas of the interferon-regulatory factor (IRF) 2 knock-out (KO) mouse represents an early phase of acute pancreatitis, including defective regulatory exocytosis, intracellular activation of trypsin, and disturbance of autophagy. The significantly upregulated and downregulated genes in the IRF2 KO pancreas have been reported. The catalogue of gene transcripts included two types of calcium-binding proteins (S100 calcium binding protein G [S100g] and Annexin A10 [Anxa10]), which were highly upregulated in the IRF2 KO pancreas. As the intracellular calcium signal plays a pivotal role in regulatory exocytosis and its disturbance is related to pancreatitis, we then evaluated the role of S100g and Anxa10 in acute pancreatitis. Method: We induced cerulein-pancreatitis in wild-type mice and examined the changes in the expression of these genes by qPCR and immunohistochemistry. We constructed S100g-overexpressing or Anxa10-overexpressing AR42J cells (AR42J-S100g, AR42J-Anxa10). We examined the changes in amylase secretion, intracellular calcium ([Ca2+]i), and cell viability in these cells, when incubated with cholecystokinin (CCK). Results: The expression of S100g and Anxa10 was increased in cerulean-induced pancreatitis. The acini were patchily stained for S100g and the cytosol of acini was evenly but weakly stained for Anxa10. Stimulation with 100pM CCK-8, decreased amylase secretion and inhibited the [Ca2+]i increase in AR42J-S100g cells. These effects were weak in AR42J-Anxa10 cells. Cell viability was not changed by incubation with cerulein. Conclusion: In cerulean pancreatitis, the expression of S100g and Anxa10 was induced in the acini. S100g may work as a Ca2+ buffer in acute pancreatitis.

70歳男性。発熱、悪寒および右季肋部痛を主訴とした。64歳時に胃癌(pStage IB)で胃全摘術(Roux-en Y再建術)を受けていた。血液検査でCRP値の軽度高値を認め、造影CTで肝S1に内部に隔壁を伴う被膜の厚い40mm大の嚢胞性病変を認めた。また、輸入脚から肝S1にかけて線状の高吸収域がみられた。以上より、輸入脚盲端異物の穿通による肝膿瘍と診断した。輸入脚盲端と肝臓は密着しており、ダブルバルーン内視鏡を用いて異物を摘出した。摘出した異物は長さ40mm、直径3mmの竹串であった。問診で3ヵ月前に泥酔状態で焼き鳥を串ごと摂取したことが判明した。術後はTAZ/PIPC投与を開始した。CRP値は低下したが、第8病日に40度台の発熱が出現し、経皮的ドレナージを施行した。その後、発熱なくCRP値が低下し、第14病日にドレーンを抜去した。第19病日に退院となり、退院後半年のCTで肝膿瘍の消失を認めた。

In this multicenter study, we evaluated the efficacy and safety of 12-week sofosbuvir/velpatasvir (SOF/ VEL) treatment. We enrolled 43 consecutive patients with decompensated cirrhosis caused by hepatitis C virus (HCV) infection, 72% and 28% of them were positive for genotype 1 and 2, respectively. At baseline, 79% of the patients were Child-Pugh (CP) class B and 19% were CP class C. All patients completed the 12-week SOF / VEL treatment without any severe adverse events. At post-treatment week 12, 41 patients achieved a sustained virological response (95%), and 21 showed improvement in CP class. The remaining two patients were lost to follow-up. Encephalopathy was a frequent adverse event (16%), but was well-controlled by outpatient management. In conclusion, 12-week SOF/VEL treatment is effective and safe for patients with decompensated cirrhosis caused by HCV infection.

33歳男性。食欲不振、関節痛を主訴に前医を受診し、A型肝炎と診断された。診断後は保存的加療にて肝酵素の改善傾向を認めたが、ビリルビン上昇が遷延し、ステロイド内服なども改善に乏しいため、黄疸遷延の加療目的に当院へ転院となった。受診時、血液検査ではビリルビンは高値を示しており、ステロイドの増量やビリルビン吸着などを検討したが、自然経過中に、ビリルビンは低下傾向となり、ステロイドの内服を継続することで、その後もビリルビン値は低下し、患者は第19病日に軽快退院後、外来での経過観察となった。

An 83-year-old man with a history of carbon ion radiotherapy for hepatocellular carcinoma nine years ago presented to a primary care hospital with a fever and abdominal pain. He underwent computed tomography, which revealed the rupture of a hepatic pseudoaneurysm close to the fiducial marker for carbon ion radiotherapy and bleeding into the bile duct. He was successfully treated with transcatheter arterial embolization. Thereafter, re-rupture occurred from a site proximal to the first rupture, and this was treated similarly. It is necessary to be alert for not only tumor recurrence but also pseudoaneurysm occurrence after carbon ion radiotherapy.

A 73-year-old man with worsened diabetes underwent abdominal computed tomography and was diagnosed with localized enlargement of the pancreatic tail. Based on the suspicion of autoimmune pancreatitis, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed. A cytologic examination showed findings suggestive of adenocarcinoma. Due to discrepancies between the imaging and pathological findings, esophagogastroduodenoscopy was performed. An extensive early gastric cancer lesion was detected in the posterior wall of the gastric corpus. It was therefore likely that puncturing through the tumor resulted in the contamination with cancer tissue. The possibility of a concomitant malignancy should be considered in EUS-FNA, and thorough examinations should be conducted.

The patient was a “73”-year-old woman who visited our hospital with the chief complaint of weight loss. Upper gastrointestinal endoscopy revealed an enlarged ampulla of Vater, and a biopsy led to a diagnosis of Group “4” gastric carcinoma suspicious of adenocarcinoma. There were no findings suggesting invasion into the muscle layer of duodenum, despite tumor mass formation being observed in the sphincter of Oddi. We performed endoscopic papillectomy for both diagnostic and therapeutic purposes. Pathologically, a well-differentiated adenocarcinoma existed in the superficial layer of the mucous membrane of the papilla of Vater, and gangliocytic paraganglioma was present in the deep portion. The resected margins of both lesions were negative.

Objectives. To evaluate the abdominal visceral fat area (VFA), we developed novel ultrasonographic (US) methods for estimating. Methods. 100 male volunteers were recruited, and their VFA was calculated by two novel US methods, the triangle method and the ellipse method. The VFA calculated by these methods was compared with the VFA calculated by CT. Results. Both the VFA calculated by the triangle method (r = 0 766, p &lt; 0 001) and the ellipse method (r = 0 781, p &lt; 0 001) showed a high correlation coefficient with the VFA calculated by CT. Also, the VFA calculated by our novel methods were significantly increased in subjects with one or more metabolic risk factors than in those without any risk factors. Furthermore, the correlation coefficients obtained using the two methods were enhanced by the addition of multiple regression analysis (with the triangle method, r = 0 8586, p &lt; 0 001; with the ellipse method, r = 0 8642, p &lt; 0 001). Conclusions. The VFA calculated by the triangle or ellipse method showed a high correlation coefficient with the VFA calculated by CT. These US methods are easy to use, they involve no radiation exposure, and the measurements can be conducted frequently. We hope that our simple methods would be widely adopted for the evaluation of VFA.

We report the case of a woman in her 40s with an asymptomatic, congenital intrahepatic portosystemic venous shunt diagnosed during a routine examination for uterine cervical cancer. Contrast-enhanced computed tomography (CT) and superior mesenteric arterial portography showed a complex intrahepatic portosystemic venous shunt with concomitant portal vein aneurysm near the hepatic hilum. The shunt appeared likely to be difficult to occlude via the usual endovascular procedure because the shunt point was narrow and short. Therefore, we performed coil embolization using a double microcatheter single vascular access technique and successfully treated without any complications.

AIM: The combination therapy of pegylated interferon-α and ribavirin (PEG IFN/RBV) is one of the effective treatments for chronic hepatitis C (CHC) patients. Natural killer (NK)-cell activity was reported to be impaired in patients with hepatitis C virus (HCV). The aim of this study was to examine whether PEG IFN/RBV therapy could restore NK activity in CHC patients. METHODS: In 19 CHC patients, PEG IFN/RBV therapy was performed. Just before (0M), at 3 months of the therapy (3M) and at 6 months after completion of the therapy (6M), NK activity and the frequency of NK cells, CD56(dim) NK cells and CD56(bright) NK cells in peripheral blood was estimated by creatinine release assay and flow cytometry. Statistical analysis was performed by anova and Mann-Whitney U-test. RESULTS: anova showed that NK activity significantly improved at 6M (vs 0M, P < 0.05) in the patients studied and in the patients with sustained virological response (SVR). It also showed that frequency of CD56(bright) NK cells was significantly increased at 6M (vs 0M, P < 0.05) in the patients studied and in the SVR group. However, no significant change in NK activity and frequency of CD56(bright) NK cells were detected in non-SVR group. Furthermore, NK activity ratio (6M/0M) in the SVR group was revealed to be higher compared with that in the non-SVR group by analysis using Mann-Whitney U-test (P < 0.05). CONCLUSION: PEG IFN/RBV therapy in CHC patients could improve NK activity by increasing the frequency of CD56(bright) NK cells in SVR patients. Our study also revealed that eradication of HCV could restore NK-cell activity.

BACKGROUND: Hepatocellular carcinoma (HCC), the fifth most common cancer type and the third highest cause of cancer death worldwide, develops in different types of liver injuries, and is mostly associated with cirrhosis. However, non-alcoholic fatty liver disease often causes HCC with less fibrosis, and the number of patients with this disease is rapidly increasing. The high mortality rate and the pathological complexity of liver diseases and HCC require blood biomarkers that accurately reflect the state of liver damage and presence of HCC. METHODS AND FINDINGS: Here we demonstrate that a circulating protein, apoptosis inhibitor of macrophage (AIM) may meet this requirement. A large-scale analysis of healthy individuals across a wide age range revealed a mean blood AIM of 4.99 ± 1.8 µg/ml in men and 6.06 ± 2.1 µg/ml in women. AIM levels were significantly augmented in the younger generation (20s-40s), particularly in women. Interestingly, AIM levels were markedly higher in patients with advanced liver damage, regardless of disease type, and correlated significantly with multiple parameters representing liver function. In mice, AIM levels increased in response to carbon tetrachloride, confirming that the high AIM observed in humans is the result of liver damage. In addition, carbon tetrachloride caused comparable states of liver damage in AIM-deficient and wild-type mice, indicating no influence of AIM levels on liver injury progression. Intriguingly, certain combinations of AIM indexes normalized to liver marker score significantly distinguished HCC patients from non-HCC patients and thus could be applicable for HCC diagnosis. CONCLUSION: AIM potently reveals both liver damage and HCC. Thus, our results may provide the basis for novel diagnostic strategies for this widespread and fatal disease.

Ultrasonography-based visceral fat estimation is a promising method to assess central obesity, which is associated with metabolic syndrome. The key to this method is to measure three types of distance in the ultrasound image. The most important one is the distance from the skin surface to the posterior wall of the abdominal aorta. We present a novel automatic measurement method to calculate this distance using 1D ultrasound signal processing. It is different from the conventional 2D image processing based methods which have high failure rate when the target is blurred or partially imaged. The proposed method identifies the waveforms of the aorta along a group of ultrasound scan lines and a rating mechanism is introduced to choose the best waveform for distance calculation. The robustness and accuracy of the method were evaluated by experiments based on clinical data.

症例は50歳の女性．繰り返す膵炎と心窩部痛の精査目的に当院紹介．造影CT，USで腫瘍や膵管・胆管拡張は認めなかったが，胆道シンチグラフィにて十二指腸への胆汁排泄遅延を認めた．入院時血液検査所見（無症状時）では肝胆道系，膵酵素，IgG4値の異常は認めなかった．ERCP所見は胆管挿管困難にてprecut施行後に胆管造影・IDUS実施したが器質的閉塞は認めなかった．主乳頭からは膵管像得られず，副乳頭からの膵管造影で背側膵管のみ造影された．膵炎の原因は膵管癒合不全と診断し，副膵管口切開術を施行した．また，biliary typeの十二指腸乳頭括約筋機能不全（SOD）も合併していると診断し，乳頭括約筋切開術も同時に施行した．その後，内視鏡的乳頭バルーン拡張術の追加を要したが，以後は膵炎の再燃も認めず自覚症状も改善している．膵管癒合不全を伴ったSODの報告は稀であり若干の文献的考察を加えて報告する．<br>

A 78-year-old man with hepatocellular carcinoma treated by chemoembolization and percutaneous ethanol injection was admitted to our hospital because of acute abdomen. The CT scan showed biliary fistula caused by hepatocellular carcinoma protruding from S3. Endoscopic retrograde cholangiopancreatography showed disruption of an intrahepatic duct and the main pancreatic duct, and contrast agent leaked into the peritoneal cavity from each duct Omental panniculitis with biliary fistula and pancreatic fistula was diagnosed. The symptoms improved by endoscopic nasobiliary drainage and endoscopic pancreatic stenting. On the 13th day after admission, we added endoscopic nasopancreatic drainage because his abdominal pain had been exacerbated by pancreatic juice leakage. Omental panniculitis by hepatocellular carcinoma complicated by biliary fistula and pancreatic fistula is extremely rare. Endoscopic transpapillary pancreaticobiliary drainage was effective for omental panniculitis in this case.

症例は73歳，男性．C型慢性肝炎にて当院通院中であった．1999年，肝細胞癌（S5単発，径3 cm）が認められ肝右葉前区域切除術を施行した．術後は4-6カ月ごとに腹部USおよびCT検査にて経過観察していた．2009年3月の腹部CT検査にて，肝右葉の手術断端に，内部が不均一で一部造影効果を示す病変が認められた．同病変は同年5月のCTにて増大傾向を認め，仮性動脈瘤と診断された．腹部血管造影では，右肝動脈の前区域枝起始部に3 cm大の仮性動脈瘤を認めた．破裂予防のため，瘤のコイル塞栓術を施行した． 仮性動脈瘤の破裂の頻度や破裂後の死亡率は高率であるため，より早期の治療が望ましいとされている．また肝癌術後の画像フォローでは，術後晩期においても再発腫瘍の有無のみならず，動脈瘤や血栓などの血管変化にも留意する必要があると考えられた．

60歳女性．突然ショック状態となり，造影CTにて脾臓および転移性肝腫瘍からの腹腔内出血と診断した．同部位に対するTAEにて血行動態は安定したが，第13病日死亡した．剖検にて腹膜播種，肝・肺・リンパ節転移をともなう脾原発血管肉腫と診断した．本疾患は原発臓器のみならず転移巣からも出血をともなうことがあり，TAEが出血性ショックに対する一時止血に有用であったと考えられ，本邦報告42例の検討とともに報告する．<br>

Background and Aim: Low levels of serum adiponectin have been reported to be associated with obesity, diabetes, and non-alcoholic steatohepatitis (NASH), as well as several malignancies. Adiponectin knockout (KO) mice have been reported to cause insulin resistance and neointimal formation of the artery. We used adiponectin KO mice fed a high fat (HF) diet, and investigated the effect of adiponectin on the progression of steatohepatitis and carcinogenesis in vivo. Methods: Adiponectin KO mice and wild type (WT) mice were fed a HF diet or normal chow for the periods of 24 and 48 weeks. The HF diet contained 60% of calories from fat. Results: The adiponectin KO mice on the HF diet showed obesity, marked elevation of serum transaminase levels, and hyperlipidemia. At 24 weeks, hepatic expression of tumor necrosis factor-alpha and procollagen alpha (I) was higher in KO mice as compared with WT mice. At 48 weeks, liver triglyceride contents in KO mice on normal chow were significantly higher than those in WT mice. Hepatocyte ballooning, spotty necrosis, and pericellular fibrosis around central veins were observed in KO mice on the HF diet. The pericellular fibrosis was more severe in KO mice on the HF diet than that in WT mice (1.62% vs 1.16%, P = 0.033). Liver adenoma and hyperplastic nodules developed in a KO mouse on the HF diet at 48 weeks (12.5%, n = 1/8), whereas no tumor was detected in WT mice (n = 10). Conclusions: Adiponectin may play a protective role in the progression of NASH in the early stages by suppressing tumor necrosis factor-alpha expression and liver fibrosis.

脂肪肉腫は大腿や後腹膜に好発するwhite adipose tissueの悪性腫瘍で，高率に再発，血行性転移がみられる．患者は60歳男性．化学療法と手術を施行し原発巣は十分にcontrolされていたが，肝に転移巣が出現した．病変は肝内に限局し，化学療法抵抗性を示したため，radiofrequency ablation（RFA）治療を行い，焼灼十分を確認した．転移性肝癌に対しても，化学療法等と組み合わせた集学的治療の一環として，RFAが有効な手段になると考えた．

脂肪肉腫は大腿や後腹膜に好発するwhite adipose tissueの悪性腫瘍で，高率に再発，血行性転移がみられる．患者は60歳男性．化学療法と手術を施行し原発巣は十分にcontrolされていたが，肝に転移巣が出現した．病変は肝内に限局し，化学療法抵抗性を示したため，radiofrequency ablation（RFA）治療を行い，焼灼十分を確認した．転移性肝癌に対しても，化学療法等と組み合わせた集学的治療の一環として，RFAが有効な手段になると考えた．<br>

The present study reports a rare case of full-blown Cushing's disease several years after an episode of pituitary apoplexy. A 60 year-old woman complained of muscular weakness and generalized malaise. Ten years ago she had an episode of pituitary apoplexy. Diabetes mellitus was diagnosed at age 56, and thereafter she had been controlled her plasma glucose with diet therapy and oral hypoglycemic agents. She exhibited cushingoid feature of moon face and central obesity. Both plasma ACTH and serum cortisol levels were elevated to 170 pg/ml and 19.6 mug/dl, respectively. Dexamethasone suppression test showed that a large dose of 8 mg dexamethasone, but not a small dose of 2 mg, suppressed the pituitary-adrenocortical axis. CRE and methyrapone caused increases in plasma ACTH and serum cortisol levels. Brain T-1-weighted magnetic resonance imaging depicted a low signal of pituitary tumor, which was not enhanced by gadolinium. The pituitary tumor was removed by transsphenoidal adenomectomy, and immunohistochemistry revealed an ACTH-producing adenoma. The evidence suggested the possibility that the two pituitary tumors with dormant period of several years were a recurrence of ACTH-producing tumors in the present patient.