肝癌致下腔静脉梗阻的内支架治疗

目的 评价肝脏肿瘤引起的下腔静脉梗阻内支架介入治疗的疗效.方法 对156例下腔静脉梗阻患者采用Z形自膨式金属内支架治疗.放置支架前后分别行下腔静脉造影,对下腔静脉狭窄或梗阻段长度、直径、压差进行分析.结果 156例患者置入179枚支架.下腔静脉狭窄或闭塞长度为(6.1±2.2)cm,狭窄段压力差由(2.1±0.5)kPa降为(0.5±0.11)kPa.狭窄段直径由(0.33±0.11)cm扩张至(1.6±0.4)cm.术后患者症状迅速改善,随访2～24个月,支架通畅率为86.7%.结论 置放Z形自膨式金属内支架,是对肝脏肿瘤引起的下腔静脉梗阻行姑息性治疗的一种有效方法.     

下腔静脉恶性梗阻的介入治疗

目的　评价采用国产金属Z形自膨胀式支架治疗下腔静脉恶性梗阻的疗效。方法78例晚期肝癌伴有下腔静脉梗阻的患者入选本研究 ,其中原发性肝癌 6 6例、转移性肝癌 12例 ,患者中男 6 6例、女 12例 ,平均年龄 (5 0 45± 11 81)岁 (年龄范围 2 0～ 78岁 )。术前所有患者均行CT、MRI或彩色超声 (以下简称彩超 )检查 ,提示下腔静脉梗阻存在 ,同时对患者的梗阻症状进行记分。经下腔静脉造影证实狭窄及其程度 ,并在狭窄段放置国产金属Z形自膨胀式支架。术前、术后分别对患者下腔静脉狭窄段内径、患者的梗阻症状积分进行比较 ,统计学处理采用配对秩和检验。术后每 2个月采用CT、彩超或下腔静脉造影对患者下腔静脉的通畅情况进行随访。结果　 78例患者下腔静脉狭窄段长度为 1 5～ 18 5cm(中位值为 7 2cm) ,共 94个支架放置于患者下腔静脉狭窄段内 ,体内支架长度为7 5～ 2 0 0cm(中位值为 10 0cm)。支架释放成功率为 98%。除 1例患者于术后第 2天出现支架内急性血栓形成外 ,其余患者术后无严重的并发症发生。下腔静脉狭窄段内径由术前 0～ 0 5cm(中位值为 0 2cm)扩张至术后 0 3～ 1 6cm(中位值为 1 0cm) (Z =- 5 4 36 5 ,P <0 0 0 0 1) ,两者差异有非常显著性意义。患者梗阻症状积分由术前的 4～ 5分 (中位值     

姑息性内支架置入术治疗累及右心房的恶性下腔静脉阻塞

目的 探讨右心房及下腔静脉内联合置入内支架治疗累及右心房的恶性下腔静脉狭窄的安全性与疗效。方法 5例男性晚期肝癌患者，年龄42－65岁，平均56．3岁，肿瘤侵及下腔静脉和右心房下腔静脉入口引起下腔静脉阻塞，产生肝肿大，腹水，下肢水肿等症状和体征，选用Z形自膨胀不锈 内支架，长度7．5－10.0cm，直径2．5cm，将其部分置入右心房，大部分置入下腔静脉，以开通阻塞的下腔静脉，心腔段内支架置入长度1－3cm，结果 内支架均置入成功，阻塞的下腔静脉全部开通，患者下腔静脉阻塞症状和体征均明显减轻或消失，随访67－188天，下腔静脉阻塞症状未见复发，也无与内支架入有关的心脏并发症，结论 对累及右心房的恶性下腔静脉狭窄采用右心房和下腔静脉联合内支架置入术是一种安全，有效的治疗方法。     

自膨式支架治疗恶性食管狭窄

目的：评价置入自膨式食管支架缓解因恶性食管狭窄引起的咽下困难的安全性和效果。方法：３６例恶性食管狭窄患者放置了自膨式金属支架，所有患者均表现为明显的咽下困难，支架置入前后行食管造影对比观察。全部操作均在Ｘ线监视下进行。结果：所有患者支架位置放置正常，无操作失误和与操作有关的并发症发生，支架置入后咽下困难立即得到明显缓解。３６例中３５例可以进正常饮食，１例进半流食。结论：自膨式支架治疗恶性食管狭窄安全，操作简单，疗效确实。食管肿瘤的生长可能引起食管再狭窄。     

肿瘤所致下腔静脉狭窄及阻塞的介入性开通治疗

目的　探讨肿瘤所致下腔静脉狭窄及阻塞的介入性开通治疗的疗效及术后处理。方法5 3例肿瘤性下腔静脉狭窄病人 ,有完整随访资料。先用导丝通过狭窄段或潜在的缝隙行球囊扩张后 ,置入支架 ,造影并测量下腔静脉压。结果　 5 3例中 5 0例开通成功 ,3例因导丝无法通过完全阻塞的下腔静脉而失败。 2例因狭窄段超过 10cm而置入 2个支架 ,其余病人均置入 1个支架。开通后下腔静脉压由术前 (2 8 6 6± 4 0 8)cmH2 O (1cmH2 O =0 0 98kPa)降至 (17 6 5± 4 18)cmH2 O ,经t检验 ,开通前后下腔静脉压变化具有非常显著性差异 (t=3 2 6 1,P <0 0 1)。 5 0例置入支架的病例中 48例下腔静脉狭窄或阻塞所致的临床症状及体征在 3～ 5d内消失或部分消失。 1例术中发生肺梗死 ,未出现其他严重并发症 ,平均随访 13 5个月 ,46例仍保持通畅。结论　支架置入治疗肿瘤性下腔静脉狭窄是一种安全有效的方法     

X线引导下金属支架置入治疗胃十二指肠恶性梗阻32例临床随访研究

目的 探讨X线引导下金属支架置入术治疗胃十二指肠恶性梗阻的临床随访与评价.方法 选取32例胃十二指肠恶性梗阻患者,行X线监视下进入导管导丝,超过狭窄或梗阻段,交换人软头超硬导丝,经超硬导丝置入并释放自膨式金属肠道支架.结果 28例患者成功置入支架,成功率为88％.术中透视造影示支架均定位准确、通畅.27例支架放置后1周内梗阻症状得到缓解或消除,临床有效率为96％.7例术后1个月左右出现梗阻复发,3例予再次放置第2枚支架后缓解.患者术后1个月生存率96％,术后2月生存率61％,术后6个月生存率25％.1例患者目前仍在随访中.结论 X线下金属支架置入治疗胃十二指肠恶性梗阻是一种可行、安全有效的方法.     

国产被覆自膨式金属内支架治疗恶性食管狭窄及食管-气管瘘

目的：评价国产被覆自膨式金属内支架治疗恶性食管狭窄及食管－气管瘘的效果和适用性。方法：利用DSA高清晰度X线电视造影、定位和监视释放。经口在0．038inch Amplatz直头导丝引导下，对食管癌引起的恶性狭窄12例置入单喇叭型；对癌性食管-气管瘘12例置入双喇叭型国产被覆自膨式金属内支架，随访3－10个月。结果：24个内支架一次性植入成功，患者可即刻吞食水，不再呛咳。结论：国产支架操作简单、 成功率高、安全、效果立竿见影，价值低廉能为众多患者接受。     

植入^125I籽源条及金属支架联合经动脉化疗栓塞治疗肝癌合并下腔静脉梗阻的初步经验

目的 报道植入~(125)Ⅰ籽源条及金属支架联合经动脉化疗栓寒治疗肝癌合并下腔静脉梗阻的初步结果.方法 自2009年3-6月,8例肝癌合并下腔静脉梗阻的患者入选本组研究,所有患者均为男性,平均年龄(61±10)岁.在患者下腔静脉梗阻段植入.~(125)Ⅰ籽源条及Z型自膨胀式金属支架,同时实施经动脉化疗栓塞术.分别对患者术前、术后下腔静脉梗阻段直径、右心房与梗阻段远端的压差及临床梗阻相关症状进行比较.术后每月对患者进行随访.结果 在下腔静脉梗阻段成功地置入8枚支架、10条~(125)Ⅰ籽源条,共植入138枚放射性~(125)Ⅰ籽源.术后患者临床症状改善显著.除1例患者术后2 d出现急性肾功能不全.其余患者无严重并发症.在平均(2.12±0.64)个月的随访期内,1例患者IVC支架发生闭塞,余患者支架保持通畅.结论 初步经验表明:植入~(125)Ⅰ籽源条及金属支架联合经动脉化疗栓塞治疗肝癌合并下腔静脉梗阻安全、可行,其远期疗效有待干进一步的研究.     

自膨胀式带膜食管支架在恶性食管狭窄患者中的应用

目的　探讨自膨胀式带膜食管支架治疗恶性食管狭窄的价值。方法　 32例晚期食管癌患者置放了自膨式带膜支架 ,全部操作在X线监视下进行 ,支架置入前后行食管造影对比观察。 16例术后接受了放疗和 (或 )化疗。所有病例均随访至死亡。结果　支架置放成功率和支架置入后患者吞咽困难缓解率均为 10 0 % ,除 5例术后 1个月内死亡外 ,术后接受放化疗者的生存时间长于未置支架者 ,两者分别为 (7.2± 6 .1)个月和 (2 .3± 1.4 )个月 (P <0 .0 5 ) ,术后 3个月再狭窄率也低于未置支架者 ,分别为 6 .3%和 5 4 .5 % (P <0 .0 5 )。结论　自膨胀式带膜食管支架治疗食管恶性狭窄疗效可靠 ,并发症少 ,术后加放疗和 (或 )化疗可进一步提高疗效     

恶性肿瘤所致上腔静脉压迫综合征的介入治疗

目的：探讨采用介入方法治疗恶性肿瘤所致上腔静脉阻塞综合征（SVCS）的疗效及临床意义。方法：24例上腔静脉阻塞综合征患者,经右侧股静脉入路,以猪尾巴导管于狭窄段近端或远端造影,明确狭窄部位、长度、程度,无局部血栓形成者直接置入Wallstent支架（Boston Scientific,USA）,合并血栓病例留置溶栓导管局部溶栓后再置入支架。结果：24例全部开通成功,手术成功率100%,狭窄段平均长度4.6 cm（3～7 cm）。3例置入2枚支架,其余患者均置入1枚支架。9例在支架置入前行溶栓治疗。开通前后梗阻远侧卧位测静脉压,术前（27.3±1.8）cmH2O,术后降至（4.5±0.8）cmH2O,置入支架后造影示侧支静脉完全消失,上腔静脉阻塞症状于术后即刻至术后3 d完全消退。随访8～26个月,11例术后5～10个月内死亡,13例存活,所有病例上腔静脉阻塞症状未再复发。结论：上腔静脉支架置入术联合导管局部溶栓是治疗恶性肿瘤所致上腔静脉阻塞综合征有效的微创治疗方法。     

Ultrasonically guided inferior vena cava stent placement: experience in 83 cases

PURPOSE: Traditionally, inferior vena cava (IVC) stent placement is performed with fluoroscopic guidance. The object of this study was to evaluate use of ultrasound (US) as guidance for IVC stent placement for the management of Budd-Chiari syndrome. MATERIALS AND METHODS: Eighty-three patients with IVC membranous stenosis (n = 30), membranous occlusion (n = 19), segmental stenosis (n = 21), or segmental occlusion (n = 13) underwent IVC recanalization, balloon dilation, and stent placement under US guidance. Among the 83 patients, 67 had at least one patent hepatic vein, while 16 patients had three occluded hepatic veins. RESULTS: IVC stents were successfully placed in 79 of 83 patients, with a success rate of 95%. After the procedure, the symptoms and signs of IVC obstruction disappeared or markedly improved in all patients, and the blockage of hepatic outflow was alleviated in 67 patients. Pericardial effusion, complete atrial ventricular block, and stent migration into the right atrium occurred, respectively, in one patient. During 1-46-month follow-up, stent restenosis occurred in one patient; the other stents remained open and functioned effectively. CONCLUSION: Because of the absence of nonionizing radiation and iodinated contrast material, and its low cost, US is well suited and often preferred for guidance of IVC stent placement.     

Ultrasonically guided percutaneous transhepatic hepatic vein stent placement for Budd-Chiari syndrome.

PURPOSE: To evaluate the utility of ultrasonically guided hepatic vein stent placement in the treatment of Budd-Chiari syndrome (BCS) in patients with short hepatic vein obstruction. MATERIALS AND METHODS: Twenty-five patients with BCS, each with three obstructed hepatic veins diagnosed with ultrasound (US), color Doppler, probing with guide wire, and echo contrast, underwent hepatic vein stent placement under US guidance. Nine patients had hepatic vein obstruction alone, and 16 had hepatic vein obstruction along with primary inferior vena cava (IVC) obstruction. In each patient, only one of the hepatic veins was selected for recanalization and stent placement. In patients with primary IVC lesions, a stent was placed in the IVC first. Clinical and US examinations were performed at 3-6-month intervals on every patient during follow-up. RESULTS: Hepatic vein stents were successfully placed in 23 of the 25 patients, a success rate of 92%. The mean +/- SD hepatic vein pressure decreased from 25.57 mm Hg +/- 9.46 to 9.67 mm Hg +/- 2.31 (P < .01), and the flow direction in the hepatic vein became centripetal and its spectral analysis showed a normal phasic flow. Twenty-two patients experienced a significant improvement in hepatic outflow, as evidenced by disappearance of ascites, remission of hepatosplenomegaly, improvement in liver function, and alleviation of esophageal varices. Severe intraperitoneal hemorrhage occurred in one patient. No other serious procedure-related complications were observed. During follow-up of 1-43 months (mean, 23 months), stent reocclusion occurred in one patient. The other stents remained patent, and clinical features of BCS did not recur. CONCLUSION: Percutaneous transhepatic hepatic vein stent placement is a reasonable treatment for BCS in patients with hepatic vein obstruction, and the procedures can be performed safely and accurately with US.     

原发性肝癌致下腔静脉阻塞的介入治疗

目的研究介入治疗肝癌所致下腔静脉梗阻的疗效及方法。方法6例患者,临床主要症状有腹胀、腹壁静脉曲张和下肢浮肿等。均为肝右叶病变压迫侵蚀下腔静脉所致的狭窄阻塞。治疗方法采用先溶栓,而后球囊扩张和内支架植入。结果6例患者狭窄阻塞的下腔静脉均开通成功,下腔静脉血流通畅,压力由术前的4.0kPa(1kPa=7.5mmHg)降至2.1kPa,无严重并发症。结论采用介入方法开通由于肝癌所引起的下腔静脉狭窄阻塞,疗效肯定,可提高患者的生活质量,延长患者的生存时间。     

Malignant gastric outlet obstructions: treatment by means of coaxial placement of uncovered and covered expandable nitinol stents

PURPOSE: To assess whether coaxial placement of uncovered and covered expandable nitinol stents overcomes the disadvantages of the increased migration rate seen with covered stents and the tumor ingrowth seen in uncovered stents in the treatment of malignant gastric outlet obstructions. MATERIALS AND METHODS: Two types of expandable nitinol stent were designed: an uncovered stent and a covered stent. Under fluoroscopic guidance, the uncovered and covered stents were placed coaxially with complete overlap in 39 consecutive patients with malignant gastric outlet obstruction caused by stomach cancer. Food intake capacity was graded on a scale of 0-4. Stent patency rate was estimated by the Kaplan-Meier method. RESULTS: Technical success rate was 97% (38 of 39 patients). After stent placement, food intake capacity improved at least one grade in 36 patients. Stent migration occurred in three patients (8%), that is, partial (n = 2) or complete (n = 1) upward migration of the inner covered stent into the stomach. Two of these patients were treated by placement of an additional covered stent. During the mean follow-up period of 134 days (range, 15-569 d), 10 patients developed recurrent symptoms of obstruction with tumor overgrowth being the most common cause. Nine underwent placement of an additional covered stent with good results. The median period of primary stent patency was 157 days (mean, 278 d). The 30-, 60-, and 180-day patency rates were 97%, 91%, and 39%, respectively. Four patients (10%) died within 1 month after the procedure. CONCLUSION: Coaxial stent placement technique seems to contribute to decreasing the migration rate of the stent and decrease the rate of recurrent obstruction by preventing or delaying tumor ingrowth.     

Retrievable covered nitinol stents: experiences in 108 patients with malignant esophageal strictures

PURPOSE: The authors report their experience with three types of retrievable covered nitinol stents in patients with malignant esophageal strictures. MATERIALS AND METHODS: Three types of retrievable covered nitinol stents were designed. Type A stents were placed in 45 patients, type B stents were placed in 29 patients, and type C stents were placed in 34 patients. The stents were removed with use of a stent retrieval set under fluoroscopic guidance when the stents caused complications. Stent patency, symptom relief, survival rate, and complications were analyzed relative to stent type and radiation therapy. RESULTS: The timing of radiation and the stent type have significant effects on occurrence of complications such as stent migration and fistula formation (P =.002 and P = 0.029, respectively). Complications were significantly more frequent in patients with the type B stent than those with type A or type C stents (P =.008). Patients who underwent radiation therapy before stent placement or who underwent no radiation therapy experienced substantially less complications than those who underwent radiation therapy after stent placement (P =.005 and P <.001, respectively). The survival period was significantly longer in patients who underwent radiation therapy after stent placement than in the other groups (P =.034). Stents were removed from 15 patients (14%) 2 days to 16 weeks (mean, 4 weeks) after stent placement as a result of severe pain (n = 7), stent migration (n = 6), or stent deformity (n = 2). Stent removal was well tolerated in all patients. CONCLUSION: Use of retrievable covered nitinol stents seems to be a safe and effective method of treatment in patients with malignant esophageal strictures. However, removal of the stents was needed in 14% of the patients because of complications. Patients who underwent radiation therapy after stent placement and those with the type B stent experienced more complications than other patients.     

Lower Extremity Venous Stent Placement: A Large Retrospective Single-Center Analysis

PurposeTo study short-term and long-term outcomes of lower extremity venous stents placed at a single center and to characterize changes in vein diameter achieved by stent placement.Materials and MethodsA database of all patients who received lower extremity venous stents between 1996 and 2018 revealed 1,094 stents were placed in 406 patients (172 men, 234 women; median age, 49 y) in 513 limbs, including patients with iliocaval stents (9.4% acute thrombosis, 65.3% chronic thrombosis, 25.3% nonthrombotic lesions). Primary, primary assisted, and secondary patency rates were assessed for lower extremity venous stents at 1, 3, and 5 years using Kaplan-Meier analyses and summary statistics. Subset analyses and Cox regression were performed to identify risk factors for patency loss. Vein diameters and Villalta scores before and up to 12 months after stent placement were compared. Complication and mortality rates were calculated.ResultsPrimary, primary assisted, and secondary patency rates at 5 years were 57.3%, 77.2%, and 80.9% by Kaplan-Meier methods and 78.6%, 90.3%, and 92.8% by summary statistics. Median follow-up was 199 days (interquartile range, 35.2–712.0 d). Patency rates for the subset of patients (n = 46) with ≥ 5 years of follow-up (mean ± SD 9.1 y ± 3.4) were nearly identical to cohort patency rates at 5 years. Patients with inferior vena cava stent placement (hazard ratio 2.11, P < .0001) or acute thrombosis (hazard ratio 3.65, P < .0001) during the index procedure had significantly increased risk of losing primary patency status. Vein diameters were significantly greater after stent placement. There were no instances of stent fracture, migration, or structural deformities. In patients with chronic deep vein thrombosis, Villalta scores significantly decreased after stent placement (from 15.7 to 7.4, P < .0001). Perioperative mortality was < 1%, and major perioperative complication rate was 3.7%.ConclusionsCavo-ilio-femoral stent placement for venous occlusive disease achieves improvement of vein disease severity scores, increase in treated vein diameters, and satisfactory long-term patency rates.     

Clinical Outcome after Intrahepatic Venous Stent Placement for Malignant Inferior Vena Cava Syndrome

We evaluated the clinical outcome of malignant inferior vena cava (IVC) syndrome after intrahepatic IVC stent placement by retrospective analysis of 50 consecutive patients (25 men, 25 women, age 32–83 years) with malignant IVC syndrome who were treated with intrahepatic stent placement. Gianturco-Rosch-Z (GRZ) stents (n = 45), and Wallstents (n = 5) were inserted. Clinical outcome was assessed from patients records using a score based on leg swelling, scrotal/vulvar edema, ascites and anasarca before and after stent placement, as well as at last follow-up visit before death. Clinical follow-up was supplemented by duplex sonography in 36 patients. Inferior venocavography was performed in 5 patients prior to re- intervention. Follow-up time ranged from 1 to 932 days (mean 62 days). Mean pressure gradient in the IVC was reduced from 14 ± 4.1 mmHg before to 2.9 ± 3.2 mmHg after stent placement (p < 0.001). Four patients had stent occlusion, 2 of whom were successfully re-stented. Primary and secondary patency was 59% and 100%, respectively at 540 days. Immediate clinical data were available in 44 patients: 38 improved; 6 did not respond. Last follow-up visit data were available in 36 patients: 24 showed persistent symptom relief till death. All symptom scores were significantly improved after stent placement (p < 0.001) and with the exception of ascites, remained significantly improved (p < 0.05) until the last follow-up. Increased serum bilirubin was a common characteristic of clinical failures and recurrences. Intrahepatic IVC stent placement resulted in significant symptomatic relief in patients with malignant IVC syndrome. Palliation was effective even in patients with a very short life expectancy.     

Anastomotic recurrence of gastric cancer after total gastrectomy with esophagojejunostomy: palliation with covered expandable metallic stents

PURPOSE: To assess the technical feasibility, safety, and clinical effectiveness of the placement of expandable metallic stents in patients with anastomotic recurrence of gastric cancer after total gastrectomy with esophagojejunostomy. MATERIALS AND METHODS: The authors retrospectively analyzed data from 32 patients in whom metallic stents were placed for recurrent obstruction after total gastrectomy with esophagojejunostomy. Technical and clinical success and complications with related interventions were evaluated. Overall survival and stent patency rates were calculated according to the Kaplan-Meier method. RESULTS: Stent placement was technically successful in 30 of the 32 patients (94%). After stent placement, 29 patients (91%) experienced improvement of their symptoms. Fourteen complications occurred after stent placement, and these consisted of pain (n = 5, 16%), stent migration (n = 3, 9%), stent obstruction due to tumor overgrowth (n = 4, 13%), and abutment of the tortuous jejunal wall by the end of the stent (n = 2, 6%). In one of five patients with pain, the stent was removed 4 hours after placement because the pain could not be controlled with analgesics. The median survival and stent patency period were 87.0 and 140.0 days, respectively. CONCLUSION: Placement of covered metallic stents in patients with anastomotic recurrence of gastric cancer after total gastrectomy with esophagojejunostomy is technically feasible, safe, and clinically effective.     

肝移植术后肝静脉和下腔静脉梗阻的诊断及介入治疗

目的 探讨肝移植术后肝静脉、下腔静脉梗阻的诊断及介入治疗技术.方法 在831例原位肝移植(OLT)、26例活体肝移植(LDLT)患者中,共有11例在移植术后2～111 d经血管造影证实为肝静脉、下腔静脉梗阻并进行了介入治疗.其中肝静脉吻合口狭窄或闭塞5例、下腔静脉吻合口狭窄5例、肝静脉狭窄伴下腔静脉吻合口狭窄1例.11例中,5例为成人OLT、4例为LDLT、2例为儿童减体积OLT,介入治疗前9例接受了肝脏CT、2例接受了MR增强扫描.术后随访患者肝肾功能指标、临床症状及肝静脉、下腔静脉血流状况.对11例患者的影像资料、介入治疗技术要点和治疗效果进行回顾性分析.介入治疗前后梗阻两端静脉压力差比较,采用配对t检验.结果 11例患者,CT或MR检查均可明确显示肝脏淤血范围、肝静脉或下腔静脉梗阻部位及程度;其中4例肝静脉梗阻和5例下腔静脉梗阻者行支架植入治疗,1例肝静脉梗阻者行经皮腔内血管球囊扩张术(PTA),1例肝静脉伴下腔静脉梗阻者,行肝静脉PTA和下腔静脉支架植入,介入治疗手术均成功.术后检测梗阻两端静脉压力差为(2.9±1.7)mm Hg(1 mm Hg=0.133 kPa),较术前(16.5±4.1)mm Hg明显下降(t=11.5,P＜0.01).术后10例患者临床症状改善,肝肾功能恢复;1例肝功能恶化,于术后第9天死于多器官功能衰竭.患者术后随访9～672 d,2例肝静脉PTA治疗者术后1个月内发生血管再狭窄,支架植入治疗者未发生再狭窄,无严重并发症发生.结论 支架植入是治疗肝移植术后肝静脉和下腔静脉梗阻安全、有效的方法;术前CT或MR对明确肝淤血范围及静脉梗阻具有重要价值.