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DNA methylation and hepatocellular carcinoma. DNA甲基化与肝细胞癌。
Pub Date : 2006-01-01 DOI: 10.1007/s00534-005-1054-4
Jingde Zhu

The epigenetic makeup of organisms forms a link between the genetic information (DNA sequence) and the gene expression (and therefore phenotype). It dictates the memory for the gene expression pattern that, in turn, specifies cell identity. DNA methylation is the most studied epigenetic mechanism, aberration of which prevails in cancer, resulting in an altered pattern of gene expression and, therefore, cancerous features, including genetic abnormalities: mutations and genome instability. Altered methylation in cancer occurs in two directions. A marked reduction in the overall level of DNA methylation has been linked to the activation of transcription/transposition and the overexpression of protooncogenes. In parallel, there is a common occurrence of a hypermethylated status of the promoter cytosine (CpG) island in genes involved in the negative control of cell growth and in the maintenance of genomic stability; therefore causing transcription silencing. It is thus necessary and important to establish a comprehensive profile of DNA methylation changes in the promoter CpG island in many genes, both for better understanding of the underlying mechanisms and for diagnostic purposes in cancer clinics. Hepatocellular carcinoma is one of the most threatening malignancies in East Asia and Africa. In this short review, I briefly outline our current understanding of DNA methylation in cancer in general, emphasizing its recent progress in hepatocellular carcinoma.

有机体的表观遗传构成在遗传信息(DNA序列)和基因表达(因此是表型)之间形成了联系。它决定了基因表达模式的记忆,进而决定了细胞的身份。DNA甲基化是研究最多的表观遗传机制,其畸变在癌症中普遍存在,导致基因表达模式改变,从而导致癌症特征,包括遗传异常:突变和基因组不稳定。癌症中甲基化的改变有两个方向。DNA甲基化总体水平的显著降低与转录/转位的激活和原癌基因的过度表达有关。与此同时,在参与细胞生长负控制和维持基因组稳定性的基因中,启动子胞嘧啶(CpG)岛的高甲基化状态也很常见;因此导致转录沉默。因此,建立许多基因启动子CpG岛DNA甲基化变化的全面概况是必要和重要的,这既可以更好地理解潜在的机制,也可以用于癌症临床诊断目的。肝细胞癌是东亚和非洲最具威胁性的恶性肿瘤之一。在这篇简短的综述中,我简要概述了我们目前对癌症中DNA甲基化的理解,并强调了其在肝细胞癌中的最新进展。
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引用次数: 43
Heterotopic gastrointestinal mucosa and pancreatic tissue in a retroperitoneal tumor. 腹膜后肿瘤的异位胃肠道黏膜和胰腺组织。
Pub Date : 2006-01-01 DOI: 10.1007/s00534-005-1089-6
Naoki Hashimoto, Kenichi Hakamada, Shunji Narumi, Eishi Totsuka, Kazunori Aoki, Yoshimasa Kamata, Mutsuo Sasaki

We believe that this is the first report of a retroperitoneal tumor consisting of heterotopic gastrointestinal mucosa and pancreatic tissue. The patient was a 19-year-old woman with the chief complaint being occasional back pain. Abdominal computerized tomography demonstrated a 3.1 x 2.5 x 3.2-cm low-density solid and cystic lesion adjoining the left renal vein between the aorta and inferior vena cava. Angiography revealed that the inferior vena cava was displaced by the hypovascular tumor. The retroperitoneal lesion was diagnosed preoperatively as a benign tumor such as a neurogenic neoplasm or lymphangioma. At laparotomy, a cystic tumor was found, which existed behind the inferior vena cava and renal vessels, and contained reddish-brown fluid, suggesting hemorrhage in the past. The cut surface of the tumor showed a unilocular cyst with partially hypertrophic wall. Histopathological examination revealed a cystic tumor lined with heterotopic gastric and duodenal mucosa, with pancreatic tissue in the muscularis propria. In addition, evidence of bleeding from the gastric mucosa was observed in the cystic tumor. External secretion from these tissues could have triggered the hemorrhage and expanded the tumor, possibly resulting in the back pain.

我们认为这是第一个由异位胃肠道黏膜和胰腺组织组成的腹膜后肿瘤的报告。患者为19岁女性,主诉为偶发背部疼痛。腹部电脑断层显示一3.1 x 2.5 x 3.2 cm的低密度实性囊性病变,位于主动脉和下腔静脉之间的左肾静脉附近。血管造影显示下腔静脉因低血管肿瘤移位。腹膜后病变术前诊断为良性肿瘤,如神经源性肿瘤或淋巴管瘤。开腹检查发现一囊性肿瘤,位于下腔静脉及肾血管后方,含红褐色液体,提示既往出血。肿瘤切面显示单眼囊肿,部分壁增厚。组织病理学检查显示一囊性肿瘤,内衬异位胃和十二指肠粘膜,胰腺组织位于固有肌层。此外,囊性肿瘤中可见胃粘膜出血的证据。这些组织的外部分泌可能引发出血并扩大肿瘤,可能导致背部疼痛。
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引用次数: 5
Assessment of hepatic reserve prior to hepatic resection. 肝切除术前肝储备的评估。
Pub Date : 2005-01-01 DOI: 10.1007/s00534-004-0950-3
Joseph J Bennett, Leslie Harold Blumgart
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引用次数: 25
Single-branch resection of the pancreas. 胰腺单支切除术。
Pub Date : 2005-01-01 DOI: 10.1007/s00534-004-0933-4
Naohiro Sata, Masaru Koizumi, Munetoshi Tsukahara, Kouji Yoshizawa, Katsumi Kurihara, Hideo Nagai

The treatment of intraductal papillary mucinous tumors (IPMT) of the pancreas is still controversial. In this report we describe a single-branch resection of the pancreas (SBRP), which is a new method for the removal of branch-type IPMT of the head of the pancreas. A multilobular cystic lesion (50 x 40 mm) in the head of the pancreas was incidentally detected in an asymptomatic 40-year-old man who underwent a routine ultrasound examination. The tumor was carefully removed along the border of the cyst and the normal parenchyma, with complete preservation of the main pancreatic duct and the common bile duct. A pancreatic fistula developed during the postoperative period, but was well-controlled by endoscopic naso-pancreatic drainage. SBRP is a technically feasible procedure and this operation represents a minimally invasive alternative to any other segmental resection of the pancreas.

胰腺导管内乳头状粘液瘤(IPMT)的治疗仍有争议。在本报告中,我们描述了胰腺单分支切除术(SBRP),这是一种去除胰腺头部分支型IPMT的新方法。一个无症状的40岁男性在接受常规超声检查时偶然发现胰腺头部多小叶囊性病变(50 x 40 mm)。沿囊肿和正常实质边界小心切除肿瘤,完整保留主胰管和胆总管。术后出现胰瘘,但经内镜下鼻胰引流术控制。SBRP是一种技术上可行的手术,该手术是任何其他胰腺节段性切除术的微创选择。
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引用次数: 11
Assessment of hepatic reserve for the indication of hepatic resection: how I do it. 肝储备对肝切除指征的评估:我是怎么做的。
Pub Date : 2005-01-01 DOI: 10.1007/s00534-004-0948-x
J Peter A Lodge

This author has personally carried out in excess of 700 major hepatic resections for tumor, and runs a unit with a current resection rate of 200 per year, yet uses no scientific tests designed to judge hepatic reserve. In our unit, we have an advantage in that we deal with a northern European population, with a low rate of viral hepatitis, although alcoholism is becoming an increasing feature within our practice and we are dealing with more elderly patients that in the past, and more who have undergone neoadjuvant chemotherapy. In these patients, there appear to be greater risks of postoperative sepsis and slower regeneration. Approximately 65% of our current resection practice is hemihepatectomy or more and the majority is trisectionectomy (extended hepatectomy) and bilateral resection work. Preoperative, operative, and postoperative factors affect the occurrence of postoperative hepatic failure and these aspects are considered. Case series studies are presented to illustrate the incidence of significant hepatic failure we have encountered.

笔者个人进行了超过700例肿瘤大肝切除术,目前每年切除200例,但没有使用科学的测试来判断肝脏储备。在我们的单位,我们的优势在于我们治疗北欧人群,病毒性肝炎发病率低,尽管酗酒在我们的实践中日益成为一个特征,我们治疗的老年患者比过去多,而且更多的患者接受了新辅助化疗。在这些患者中,术后脓毒症的风险更大,再生速度更慢。我们目前大约65%的切除是半肝或更多的切除,大多数是三节切除术(扩展肝切除术)和双侧切除工作。术前、手术和术后因素影响术后肝功能衰竭的发生,并考虑这些方面。案例系列研究提出,以说明发生率显著肝功能衰竭,我们已经遇到。
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引用次数: 5
Assessment of hepatic reserve for the indication of hepatic resection. 肝储备对肝切除指征的评估。
Pub Date : 2005-01-01 DOI: 10.1007/s00534-004-0951-2
Jaques Belghiti, Satoshi Ogata

The main goal of liver resection in patients with liver tumor is to cure the patients with the lowest operative risk. Based on our experiences, we report herein, indications of liver resection according to the nature of underlying liver parenchyma. In patients with normal underlying liver parenchyma, major resection does not require specific preoperative assessment. Non-tumorous biopsy is indicated in cases of massive steatosis and/or in patients in whom a complex technical procedure is anticipated. Portal vein embolization (PVE) is considered if the future liver remnant (FLR) is < 30%. In patients with chronic liver disease, major hepatectomy is a risky situation, requiring specific preoperative assessment, including non-tumorous biopsy and PVE which could be associated with transarterial chemoembolization. Absence of hypertrophy of the FLR after PVE is a contraindication to a major hepatectomy. Intraoperative procedures in patients "at risk" require specific techniques, including intermittent clamping, anterior approach with hanging maneuver, and fixation on anatomical position of the remnant liver.

肝肿瘤患者肝切除术的主要目的是治愈手术风险最低的患者。根据我们的经验,我们在此报告肝切除的指征,根据肝实质的性质。对于正常的肝实质患者,大切除不需要术前评估。非肿瘤活检适用于大量脂肪变性和/或需要进行复杂技术手术的患者。如果未来肝残余(FLR) < 30%,则考虑门静脉栓塞(PVE)。对于慢性肝病患者,大肝切除术是一种危险的情况,需要具体的术前评估,包括非肿瘤活检和PVE,这可能与经动脉化疗栓塞有关。PVE术后FLR无肥厚是大肝切除术的禁忌症。“有危险”患者的术中操作需要特定的技术,包括间歇夹持、悬挂手法前路入路和残肝解剖位置固定。
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引用次数: 51
A scoring system for the assessment of the risk of mortality after partial hepatectomy in patients with chronic liver dysfunction. 慢性肝功能不全患者部分肝切除术后死亡风险评估的评分系统。
Pub Date : 2005-01-01 DOI: 10.1007/s00534-004-0953-0
Ikuo Nagashima, Tadahiro Takada, Kota Okinaga, Hirokazu Nagawa

Background/purpose: The aim of this study is to evaluate a new scoring system, called the chronic liver dysfunction (CLD) score, for prediction of the surgical risk of partial hepatectomy in patients with chronic liver damage. Morbidity and mortality rates after gastroenterological surgery are high in patients with hepatic cirrhosis. Accordingly, it is very important to assess the surgical risk in such patients before surgery. Although the Child classification (or Child-Pugh score) has been a standard system, it did not always accurately predict patients at the risk of mortality after gastroenterological surgery, especially partial hepatectomy.

Methods: In 1985, we established a new system called the CLD score, reviewing the patients undergoing gastroenterological operations at one hospital. In the present study, we prospectively used the CLD score in 256 consecutive patients with chronic liver dysfunction who were treated surgically by partial hepatectomy, and investigated the usefulness of the CLD score concerning mortality. The results were compared with those of the Child-Pugh score (C-P score).

Results: After major hepatectomy, all the patients with CLD score exceeding 1.5 died of hepatic failure. After minor hepatectomy, all the patients with CLD score exceeding 2.5 died of hepatic failure. On the other hand, C-P score did not predict the outcome in these patients.

Conclusions: Compared with the C-P score, which was considered the gold standard scoring system for assessing surgical risk for patients with chronic liver dysfunction, our CLD score provides a more reliable assessment of the risk of partial hepatectomy.

背景/目的:本研究的目的是评估一种新的评分系统,称为慢性肝功能障碍(CLD)评分,用于预测慢性肝损害患者部分肝切除术的手术风险。肝硬化患者在胃肠外科手术后的发病率和死亡率都很高。因此,术前评估此类患者的手术风险是非常重要的。虽然Child分类(或Child- pugh评分)已经成为一个标准系统,但它并不总是准确地预测患者在胃肠外科手术后的死亡风险,特别是部分肝切除术。方法:1985年,我们建立了一种新的CLD评分系统,对一家医院接受胃肠外科手术的患者进行评分。在本研究中,我们前瞻性地对256例经部分肝切除术治疗的连续慢性肝功能障碍患者使用CLD评分,并研究CLD评分与死亡率的相关性。将结果与Child-Pugh评分(C-P评分)进行比较。结果:大肝切除术后,CLD评分超过1.5分的患者均死于肝功能衰竭。小肝切除术后,CLD评分超过2.5的患者均死于肝功能衰竭。另一方面,C-P评分并不能预测这些患者的预后。结论:与被认为是评估慢性肝功能障碍患者手术风险的金标准评分系统C-P评分相比,我们的CLD评分对肝部分切除术的风险提供了更可靠的评估。
{"title":"A scoring system for the assessment of the risk of mortality after partial hepatectomy in patients with chronic liver dysfunction.","authors":"Ikuo Nagashima,&nbsp;Tadahiro Takada,&nbsp;Kota Okinaga,&nbsp;Hirokazu Nagawa","doi":"10.1007/s00534-004-0953-0","DOIUrl":"https://doi.org/10.1007/s00534-004-0953-0","url":null,"abstract":"<p><strong>Background/purpose: </strong>The aim of this study is to evaluate a new scoring system, called the chronic liver dysfunction (CLD) score, for prediction of the surgical risk of partial hepatectomy in patients with chronic liver damage. Morbidity and mortality rates after gastroenterological surgery are high in patients with hepatic cirrhosis. Accordingly, it is very important to assess the surgical risk in such patients before surgery. Although the Child classification (or Child-Pugh score) has been a standard system, it did not always accurately predict patients at the risk of mortality after gastroenterological surgery, especially partial hepatectomy.</p><p><strong>Methods: </strong>In 1985, we established a new system called the CLD score, reviewing the patients undergoing gastroenterological operations at one hospital. In the present study, we prospectively used the CLD score in 256 consecutive patients with chronic liver dysfunction who were treated surgically by partial hepatectomy, and investigated the usefulness of the CLD score concerning mortality. The results were compared with those of the Child-Pugh score (C-P score).</p><p><strong>Results: </strong>After major hepatectomy, all the patients with CLD score exceeding 1.5 died of hepatic failure. After minor hepatectomy, all the patients with CLD score exceeding 2.5 died of hepatic failure. On the other hand, C-P score did not predict the outcome in these patients.</p><p><strong>Conclusions: </strong>Compared with the C-P score, which was considered the gold standard scoring system for assessing surgical risk for patients with chronic liver dysfunction, our CLD score provides a more reliable assessment of the risk of partial hepatectomy.</p>","PeriodicalId":15992,"journal":{"name":"Journal of hepato-biliary-pancreatic surgery","volume":"12 1","pages":"44-8"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00534-004-0953-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24994495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 28
Assessment of hepatic reserve for indication of hepatic resection: how I do it. 肝储备对肝切除指征的评估:我是怎么做的。
Pub Date : 2005-01-01 DOI: 10.1007/s00534-004-0947-y
Wei-Chen Lee, Miin-Fu Chen

Background/purpose: Hepatic resection may result in liver failure in patients with cirrhotic livers. Preoperative evaluation of liver function in cirrhotic patients, to prevent postoperative liver failure, is very important.

Methods: Sixteen patients with hepatocellular carcinoma in cirrhotic livers were enrolled in this study. Liver function was determined quantitatively by monoethylglycinexylidide (MEGX) formation from the metabolism of lidocaine. The whole liver volume and tumor volume were measured by computed tomographic volumetry. The volume of resected liver was recorded by water displacement. The relationship between liver function and remnant liver volume was determined.

Results: A relationship between the percentage remnant liver volume and ratio of MEGX formation after hepatectomy was found. The regression equation was: (postoperative MEGX formation/preoperative MEGX formation) x 100% = (0.688 x percentage remnant liver volume + 0.179) x 100% (r (2) = 0.49). A relationship between MEGX formation after hepatectomy and the international ratio (INR) of prothrombin time was also found. The regression equation was INR = 1.99 - 0.01 x MEGX (r (2) = 0.30).

Conclusions: Post-hepatectomy liver function can be estimated for an individual patient by the appropriate regression equations. Prevention of post-hepatectomy liver failure for patients with cirrhotic livers is feasible.

背景/目的:肝切除术可能导致肝硬化患者肝功能衰竭。术前评估肝硬化患者肝功能,对预防术后肝功能衰竭,具有十分重要的意义。方法:选取16例肝硬化肝细胞癌患者为研究对象。通过利多卡因代谢产生的单乙基甘氨酸乙酯(MEGX)定量测定肝功能。采用计算机断层体积仪测量全肝体积和肿瘤体积。用排水量法记录切除肝脏的体积。测定肝功能与残肝体积的关系。结果:肝切除术后残肝体积百分比与MEGX形成率呈正相关。回归方程为:(术后MEGX形成/术前MEGX形成)x 100% = (0.688 x残肝体积百分比+ 0.179)x 100% (r(2) = 0.49)。肝切除术后MEGX的形成与凝血酶原时间的国际比(INR)也有关系。回归方程为INR = 1.99 - 0.01 × MEGX (r(2) = 0.30)。结论:肝切除术后患者的肝功能可以通过适当的回归方程来估计。预防肝硬化患者肝切除术后肝功能衰竭是可行的。
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引用次数: 12
A minute nonfunctioning islet cell tumor demonstrating malignant features. 一分钟无功能的胰岛细胞肿瘤,表现出恶性特征。
Pub Date : 2005-01-01 DOI: 10.1007/s00534-004-0938-z
Naoki Ikenaga, Koji Yamaguchi, Hiroyuki Konomi, Kei Fujii, Atsushi Sugitani, Masao Tanaka

We report a patient with a minute nonfunctioning islet cell tumor, 8 mm in diameter, which demonstrated malignant features by histology. The patient was a 43-year-old Japanese woman, who had an elevated carbohydrate antigen (CA) 19-9 level, of 59 U/ml (normal range, <37 U/ml) identified on a health check to rule out malignancies. Ultrasonography and computed tomography demonstrated a well-defined pancreatic tumor, 8 mm in diameter, in the body of the pancreas. Serum levels of pancreatic hormones were within normal limits, and thus a tentative diagnosis was nonfunctioning islet cell tumor. The size of the tumor remained unchanged for 1 1/2 years, but, at this time, the serum level of CA19-9 was elevated to 253 U/ml. Segmental pancreatectomy was performed because malignancy could not be ruled out. The resected specimen showed an endocrine tumor invading both the pancreatic parenchyma and the perineural spaces outside the tumor. In general, minute nonfunctioning islet cell tumors have been considered to be completely benign, but the present tumor showed clear malignant features. We might have to take surgical resection into consideration even if the size of such an endocrine tumor is minute.

我们报告一个病人与一个微小的无功能的胰岛细胞肿瘤,直径8毫米,表现出恶性特征的组织学。患者为一名43岁的日本女性,碳水化合物抗原(CA) 19-9水平升高,59 U/ml(正常范围)。
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引用次数: 9
Complete obstruction of the lower common bile duct caused by autoimmune pancreatitis: is biliary reconstruction really necessary? 自身免疫性胰腺炎引起的胆总管下段完全梗阻:胆道重建真的有必要吗?
Pub Date : 2005-01-01 DOI: 10.1007/s00534-004-0937-0
Toshiki Matsubara, Yoichi Sakurai, Hirotake Miura, Hidetaka Kobayashi, Mitsutaka Shoji, Yasuko Nakamura, Hiroki Imazu, Shigeru Hasegawa, Masahiro Ochiai, Takahiko Funabiki

Recent observations suggest that an immune response is involved in the development of chronic pancreatitis. We report a case of autoimmune pancreatitis in a patient who showed complete obstruction of the lower common bile duct. A 63-year-old man was admitted to a local hospital, complaining of appetite loss and back pain. The patient had obstructive jaundice, and percutaneous transhepatic gallbladder drainage was performed. Fluorography through the biliary drainage catheter showed complete obstruction of the lower common bile duct. The patient had no history of alcohol consumption and no family history of pancreatic disease. Physical examination revealed an elastic hard mass palpable in the upper abdomen. Abdominal ultrasound and abdominal computed tomography (CT) scans showed enlargement of the pancreas head. While autoimmune pancreatitis was highly likely, due to the patient's high serum immunoglobulin level, the possibility of carcinoma of the pancreas and/or lower common bile duct could not be ruled out. Laparotomy was performed, and wedge biopsy samples from the pancreas head and body revealed severe chronic pancreatitis with infiltration of reactive lymphocytes, a finding which was compatible with autoimmune pancreatitis. Cholecystectomy and biliary reconstruction, using choledochojejunostomy, were performed, because the complete bile duct obstruction was considered to be irreversible, due to severe fibrosis. After the operation, prednisolone (30 mg/day) was given orally for 1 month, and the entire pancreas regressed to a normal size. Complete obstruction of the common bile duct caused by autoimmune pancreatitis has not been reported previously; this phenomenon provides an insight into autoimmune pancreatitis and provokes a controversy regarding whether biliary reconstruction is needed for the treatment of complete biliary obstruction caused by autoimmune pancreatitis.

最近的观察表明,免疫反应参与慢性胰腺炎的发展。我们报告一例自身免疫性胰腺炎患者表现为胆总管下段完全梗阻。一名63岁的男子因食欲不振和背部疼痛被当地一家医院收治。患者为梗阻性黄疸,行经皮肝胆囊引流术。胆道引流管造影显示胆总管下段完全梗阻。患者无饮酒史,无胰腺疾病家族史。体格检查显示在上腹部可触及一弹性硬块。腹部超音波及腹部电脑断层扫描显示胰头肿大。虽然自身免疫性胰腺炎的可能性很大,但由于患者血清免疫球蛋白水平较高,不能排除胰腺癌和/或胆总管下段癌的可能性。进行剖腹手术,胰腺头部和胰腺体的楔形活检显示严重的慢性胰腺炎伴反应性淋巴细胞浸润,这一发现与自身免疫性胰腺炎相一致。由于胆管梗阻严重纤维化,被认为是不可逆的,因此采用胆总管空肠吻合术进行胆囊切除术和胆道重建。术后给予强的松龙(30 mg/天)口服1个月,整个胰腺恢复正常大小。自身免疫性胰腺炎引起的胆总管完全梗阻此前未见报道;这一现象为自身免疫性胰腺炎的研究提供了新的视角,也引发了关于自身免疫性胰腺炎引起的完全性胆道梗阻是否需要胆道重建的争议。
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引用次数: 10
期刊
Journal of hepato-biliary-pancreatic surgery
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