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1.
BACKGROUND: Secondary hyperparathyroidism (2HPT) is a frequent complication of long-term dialysis treatment and, despite recent advances in medical therapy, surgical parathyroidectomy (PTX) is required in a considerable number of uraemic patients. Recently, other modalities of therapy, such as ultrasound-guided percutaneous parathyroid injection of ethanol (PEIT) or of calcitriol (PCIT), have been used to treat refractory 2HPT. Our objectives were to evaluate the efficacy of these therapeutic modalities and to analyse their effects on parathyroid cell proliferation. METHODS: Nineteen haemodialysis patients with severe 2HPT were studied. Ten underwent PEIT (Group I) and nine underwent PCIT (Group II). After treatment, five patients in each group were submitted to PTX. Parathyroid cell proliferation was appraised at the beginning and at the end of the study by fine-needle aspiration biopsy, making use of immunocytochemical testing for Ki-67. The surgically removed glands were submitted to histopathological analysis and cellular proliferation was evaluated. RESULTS: Both PEIT and PCIT proved inefficient in controlling 2HPT. Comparing study onset with day 60, both groups showed a significant decrease in serum-ionized calcium: 5.3+/-0.3 vs 5.1+/-0.5 mg/dl (P = 0.03) in Group I and 5.5+/-0.4 vs 5.4+/-0.3 mg/dl (P = 0.03) in Group II. Other laboratory parameters were unchanged. There was a significant, although transitory, enlargement in glandular volume in Group II at day 30 when compared with study onset (1.5+/-0.6 vs 1.7+/-0.7 cm(3), P = 0.02). When comparing the two groups, Group I showed a glandular volume smaller than that of Group II at days 30 (1+/-0.5 vs 1.7+/-0.7 cm(3), P = 0.003), 60 (0.8+/-0.4 vs 1.5+/-0.9 cm(3), P = 0.006) and 90 (0.8+/-0.5 vs 1+/-0.7 cm(3), P = 0.02). Cellular proliferation, which was equally elevated in both groups at the beginning of the study, could not be evaluated at the end due to lack of material. The majority of glands obtained through PTX presented intensive cellular proliferation and contained areas of nodular hyperplasia, even those glands with a volume of <0.5 cm(3). CONCLUSION: In our experience, both PCIT and PEIT were unable to control severe 2HPT in chronic haemodialysis patients. We believe that the severity of the 2HPT in the study patients, in conjunction with the fact that we excluded from treatment parathyroid glands with a volume of <0.5 cm(3), were the most important causes of this failure.  相似文献   

2.
BACKGROUND: Percutaneous ethanol injection therapy (PEIT) is used for advanced secondary hyperparathyroidism. We investigated the efficacy, remission period and risk of relapse to determine the effect of the number of hyperplastic glands and other factors on the therapeutic effect of PEIT. METHODS: We studied 321 patients divided into two groups: effective [serum corrected calcium (cCa) level < or =10.5 mg/dl and serum intact parathyroid hormone (iPTH) level < or =250 pg/ml], and ineffective (failed to achieve the target levels). Advanced hyperplasia was defined as an estimated volume > or =0.5 cm(3) on ultrasonography. RESULTS: PEIT was effective in 201 patients (62.6%), in whom serum iPTH levels dropped from 603+/-292 to 183+/-62 pg/ml (ng/l) and serum cCa levels from 10.7+/-0.8 to 10.1+/-0.5 mg/dl. Univariate analysis identified age, the number of hyperplastic glands and iPTH level as factors related to the efficacy of PEIT. The odds ratio for success vs failure by multivariate analysis was 0.55 times for the number of hyperplastic glands > or =0.5 cm(3) (> or =2 vs 0,1) and 0.29 times for iPTH (> or =500 vs <500 pg/ml). Using the Kaplan-Meier method, the number of hyperplastic glands > or =0.5 cm(3) (> or =2 vs 0,1) was a factor affecting the remission period, with a remission significantly longer seen in the group with one hyperplastic gland (P=0.0025). CONCLUSIONS: Superior results in efficacy rate, remission period and risk of relapse are obtained when PEIT is restricted to patients with one hyperplastic gland > or =0.5 cm(3).  相似文献   

3.
Persistent hyperparathyroidism is frequent in postrenal transplant patients. Percutaneous ethanol injection therapy (PEIT) is an alternative for treatment of patients with secondary hyperparathyroidism but it was not described in postrenal transplant patients. We report our experience with PEIT to control hyperparathyroidism in the post-transplant period. We performed PEIT under ultrasonographic guidance and local anesthesia in eight patients because of persistent secondary hyperparathyroidism after renal transplantation. Indications for PEIT were: high intact parathyroid hormone (iPTH) levels with hypercalcemia, hypophosphatemia, osteopenia and/or bone pain. All patients had at least one visible parathyroid nodule by ultrasonography. Biochemical assays were performed immediately before PEIT, between 1 and 7 days after last PEIT, and a mean of 8.0 +/- 2.8 months after PEIT. Serum iPTH and calcium levels decreased significantly after treatment and remained unchanged until final control. Serum iPTH decreased from 286.9 +/- 107.2 to 154.6 +/- 42.2 pg/ml (P < 0.01) after PEIT (percentual reduction 36.5 +/- 9.5%). This response was significantly correlated to total ethanol volume used (r: 0.94, P < 0.0001). Hypercalcemia disappeared in six of eight patients treated. Only minor complications were registered. There were no changes in renal function related to the treatment. Our findings show that PEIT is a useful and safe alternative for patients with persistent post-transplant secondary hyperparathyroidism.  相似文献   

4.
Chen HH  Chen YC  Yeh JC 《Nephron》2002,92(1):105-110
What could be done for patients with chronic renal failure are marginally beneficial. Among 58 pre-dialysis patients, we found 24 of chronic glomerulonephritis (CGN) with serum creatinine >5 mg/dl and intact parathyroid hormone (i-PTH) >200 pg/ml. In this study, we determined if the residual renal function could be preserved when hyperparathyroidism was corrected by either low-dose calcitriol treatment or ethanol injection. The 58 CGN patients were divided into three groups. The first group, which comprised 11 cases with i-PTH >200 pg/ml and had parathyroid mass, were treated by ultrasonography-guided percutaneous ethanol injection therapy (PEIT). The second study group composed of 13 cases with i-PTH >200 pg/ml without parathyroid mass were treated by calcitriol 1 microg every other day. The third group made up of 34 cases with i-PTH <200 pg/ml, who did not receive calcitriol or ethanol therapy. All patients were followed up within 2 years or until dialysis. The average rate of decline in renal function (slope of reciprocal serum creatinine vs. time) was 0.0025 +/- 0.0026 dl/mg month in group 1, 0.0054 +/- 0.0024 in group 2, and 0.0067 +/- 0.0025 in group 3 (p = 0.018 in group 1 vs. group 2, p < 0.001 in group 1 vs. group 3). The declines of i-PTH, phosphorus, and alkaline phosphatase, and the increase of calcium were all significantly different between group 1 and group 3. Two cases of group 1, 6 cases of group 2, and 20 cases of group 3 entered into dialysis during this study. In conclusion, selective PEIT guided by color Doppler flow mapping is an effective therapy for treating hyperparathyroidism and protecting the residual renal function.  相似文献   

5.
A 15-year-old boy with chronic renal failure secondary to Alport’s syndrome underwent living-related renal transplantation from his 48-year-old father. His primary immunosuppressive regimen was composed of tacrolimus, mizolibine, and methylprednisolone. The postoperative course was satisfactory with one episode of mild acute rejection, treated successfully with methylprednisolone pulse therapy. Two months later, hypercalcemia (11.8–13.2 mg/dl) and hypophosphatemia (2.5–3.0 mg/dl) were noted without any bone symptoms. The serum intact-parathyroid hormone (PTH) and serum alkaline phosphatase levels were 240 pg/ml and 2483 IU/l, respectively. Ultrasound studies revealed enlargement of the two parathyroid glands. Under the diagnosis of ter-tiary hyperparathyroidism, he underwent percutaneous ethanol injection (PEIT) into the left parathyroid gland. Although levels of serum calcium and phosphorus returned to normal ranges and the intact PTH level decreased to 95 pg/ml with the three injections, another injection was needed to normalize recurrent hypercalcemia 2 months later. The patient experienced only transient mild dysphonia and local pain after PEIT. Although PEIT is believed less effective than parathyroidectomy, it has some advantages such as applicability to high-risk patients, repeatability of treatment, low incidence and severity of side effects. Received: 26 June 2001 / Revised: 21 November 2001 / Accepted: 24 November 2001  相似文献   

6.
7.
Two chronic hemodialysis patients had recurrent, severe secondary hyperparathyroidism. The first had no sonographically visible parathyroid gland in the neck. Computed tomography (CT) scan indicated the existence of a parathyroid mass in the upper mediastinum, which was removed surgically. The second patient had two intracervical, hyperplastic parathyroid glands visible on ultrasound examination. He volunteered for nonsurgical removal via sonographically guided percutaneous injection of ethanol. In both patients, serum total calcium concentration decreased dramatically to values near 1.5 mmol/L 24 hours after treatment. In patient 1, serum immunoreactive parathyroid hormone (iPTH) (1-84) decreased from 1,582 pg/mL before surgery to 34 pg/mL after 24 hours (normal range, 10 to 65 pg/mL). In contrast, serum iPTH (1-84) decreased only progressively in patient 2, from 1,680 pg/mL before ethanol injection to 865 pg/mL after 24 hours and to 378 pg/mL after 72 hours to reach 30 pg/mL after 14 days. Thus, patient 2 had a striking decrease of plasma calcium immediately after parathyroid gland destruction, even though circulating iPTH was still very high. The reason for such a discrepancy remains unexplained at present, and further study will be necessary to solve this issue.  相似文献   

8.
Background. Tertiary hyperparathyroidism continues to cause significant morbidity in patients with chronic renal failure. This is frequently resistant to medical management and may ultimately require a surgical parathyroidectomy. Recent studies have reported upon the technique of percutaneous ethanol ablation for both primary and tertiary hyperparathyroidism. In this study we report on a 5 year experience using ethanol injection and compare the results with surgical parathyroidectomy. Methods. A prospective study in 39 patients with tertiary hyperparathyroidism, 25 were dialysis dependent and 14 had a functioning renal allograft. Twenty-two patients underwent percutaneous fine needle ethanol injection (PFNEI) and 17 underwent surgical parathyroidectomy. Results. A >30% reduction in intact parathyroid hormone (iPTH) was achieved in 11 of 22 patients undergoing PFNEI after a mean of 1.8±1.4 injections per gland. In four patients, symptomatic hyperparathyroidism recurred and they required further PFNEI or surgical parathyroidectomy at 17, 28, 46, and 48 months later. There was no significant reduction in iPTH in 11 patients following PFNEI after a mean of 2.5±1.3 injections per gland. They all required a subsequent surgical parathyroidectomy for symptomatic hyperparathyroidism. Four patients developed a laryngeal nerve palsy following PFNEI, two of which were permanent. Seventeen patients underwent successful surgical parathyroidectomy as a primary procedure. Conclusion. Whilst PFNEI is successful in primary hyperparathyroidism, when typically only one adenoma is present, the effectiveness of PFNEI is unpredictable and the long term results are poor compared with those of surgical parathyroidectomy in tertiary hyperparathyroidism. The procedure is not without complications and makes subsequent surgery more difficult. Therefore it can only be recommended for patients with a known single parathyroid gland such as patients in whom hyperparathyroidism has recurred following a previous surgical subtotal parathyroidectomy and who are unsuitable for further surgery.  相似文献   

9.
10.
11.
BACKGROUND: Percutaneous ethanol injection treatment (PEIT) has been proposed as an alternative to surgery for patients with secondary hyperparathyroidism. The present study was undertaken to determine factors that may predict results. METHODS: We performed PEIT in 19 patients with secondary hyperparathyroidism refractory to medical therapy under ultrasonographic guidance in an ambulatory facility with local anesthesia. Biochemical assays were performed immediately before the last dialysis session (basal) and between 1 to 7 days after PEIT (post-PEIT). RESULTS: Serum PTH, calcium, and phosphorus levels decreased significantly after treatment. The percent of change in serum PTH was significantly correlated to total nodular volume (r = 0.73, P = 0.0004), and basal PTH levels (r = 0.48, P = 0.03). Post-PEIT serum phosphate and calcium x phosphate product disclosed negative correlations that were statistically significant with the decrease of PTH levels (r = -0.60, P = 0.009, and r = -0.60, P = 0.01, respectively). The total nodular volume was significantly correlated to the percent change in serum calcium levels (r = 0.60, P = 0.01), in phosphate levels (r = 0.64, P = 0.009), and calcium x phosphate product (r = 0.66, P = 0.01). CONCLUSION: Our findings suggest that patients with uncontrolled secondary hyperparathyroidism may benefit from PEIT if they present with very high basal PTH levels and/or big nodule size.  相似文献   

12.
目的应用彩色多普勒超声对继发甲状旁腺机能亢进超声引导无水酒精治疗的疗效进行观察。方法对38个增生的甲状旁腺腺体进行超声引导下注射无水酒精治疗,分别于治疗前及治疗后1个月用彩色多普勒超声观察甲状旁腺的回声,体积和血供变化情况。结果增生的甲状旁腺在治疗前回声呈均匀一致的低回声,腺体内血供丰富。当注射无水酒精后,腺体内立即呈略强回声,血供明显减少甚至消失。术后1个月复查,腺体内回声多呈略强回声,部分腺体回声恢复到治疗前的水平。治疗前后腺体体积改变无显著性差异(P>0.05)。结论彩色多普勒超声对继发甲状旁腺机能亢进超声引导下注射无水酒精的疗效前后观察具有重要价值。  相似文献   

13.
The authors encountered a 2-year-old-girl with adrenocortical carcinoma who underwent percutaneous ethanol injection therapy (PEIT) for liver metastasis. The patient had functional adrenocortical carcinoma diagnosed and underwent excision of the tumor in the right adrenal gland. Because liver metastasis was detected 11 months after surgery, the patient underwent PEIT under general anesthesia. After the treatment, the size of the metastatic tumor was reduced with calcification and then disappeared. The patient was in a good condition 3 years, 3 months after the occurrence of liver metastasis.  相似文献   

14.
A 44 year-old woman was diagnosed as having chronic renal failure due to rapidly progressive glomerulonephritis (RPGN) from one year earlier. She has been managed with steroid therapy and hemodialysis. The patient was admitted to our hospital because of fever and sudden disturbance of consciousness with generalized convulsion on October 30, 2003. She showed mild meningeal irritation. Cerebrospinal fluid (CSF) examination demonstrated a cell count of 60/microl, protein level of 70 mg/dl, glucose level of 52 mg/dl, and chloride (Cl) level of 116 mEq/l. Both the CSF culture for Mycobacterium (M.) tuberculosis and the conventional single polymerase chain reaction (PCR) for M. tuberculosis DNA in CSF were negative results on admission. In contrast, nested PCR of preserved CSF samples obtained at admission demonstrated positive results. We diagnosed her conditions as tuberculous meningitis (TBM) and administered a total of 3 anti-tuberculosis agents over a period of about 2 months. Her clinical condition and CSF examinations improved immediately in response to anti-tuberculosis treatment. Serial CSF cultures for M. tuberculosis and the serial single PCRs for M. tuberculosis DNA in CSF were all negative during the course of anti-tuberculosis treatment. However, serial nested PCR results gradually converted from positive to negative, correlating with the improvement in clinical conditions during the course of anti-tuberculosis treatment. Therefore, nested PCRs were much more useful for the rapid and accurate diagnosis of TBM and for assessment of the clinical course and anti-tuberculosis treatment response of TBM than conventional CSF cultures and single PCRs. To the best of our knowledge, there have been few previous reports of diachronic study in which the serial nested PCR was used to test CSF samples obtained earlier in the clinical course of TBM. In conclusion, our findings suggest that nested PCR for M. tuberculosis DNA in CSF was highly useful not only for rapid and accurate diagnosis of TBM, but also for assessment of the antituberculous treatment response in cases highly suspected of TBM despite negative results on conventional cultures and single PCRs.  相似文献   

15.
AIMS: This 1-year double-blind, placebo-controlled, multicenter study evaluated the long-term safety and efficacy of cinacalcet for the treatment of secondary hyperparathyroidism in patients receiving hemodialysis. METHOD: Patients were randomly assigned in a 1:1 ratio to cinacalcet or control treatment groups. The initial dose of cinacalcet (or matching placebo) was 30 mg. Doses were titrated every 3 or 4 weeks based on the intact parathyroid hormone (iPTH) response and safety profile. Sequential doses included 30, 60, 90, 120 and 180 mg/d. Phosphate binders and vitamin D sterols were adjusted per protocol as needed to control levels of calcium and phosphorus. Efficacy and safety were compared between treatment groups among patients who completed the study (52 total weeks of treatment). Reasons for withdrawal are presented for patients who did not complete the study. RESULTS: A total of 210 patients completed 52 weeks of double-blinded treatment with cinacalcet (n = 99) or placebo (n = 111). Over the last 6 months of the study, a greater proportion of patients in the cinacalcet group than the control group achieved an iPTH level < or = 250 pg/ml (61.6 vs. 9.9%, p < 0.001) or a > or = 30% decrease in iPTH from baseline (81.8 vs. 21.6%, p < 0.001). Mean iPTH levels decreased by -47.8% in the cinacalcet group and increased by +12.9% in the control group. Mean percentage changes in other laboratory values in the cinacalcet and control groups included the following: serum calcium -6.5 vs. +0.9% (p < 0.001), serum phosphorus -3.6 vs. -1.1% (p = 0.465), and Ca x P -9.9 vs. -0.3% (p = 0.006). The most commonly reported adverse events related to study drug by the investigators included nausea (13% cinacalcet, 5% control), investigator-reported hypocalcemia (11% cinacalcet, 1% control), vomiting (9% cinacalcet, 2% control), dyspepsia (5% cinacalcet, 4% control), and diarrhea (5% cinacalcet, 2% control). CONCLUSIONS: Treatment with cinacalcet is a safe and effective therapy for long-term control of secondary hyperparathyroidism. 1-year therapy with cinacalcet was associated with sustained, clinically significant reductions in calcium, Ca x P and iPTH which allowed a greater percentage of patients to achieve NKF-KDOQI target goals for PTH and Ca x P.  相似文献   

16.
BACKGROUND: Although vitamin D has been reported to be useful in the treatment of patients with secondary hyperparathyroidism, it is not effective in some of them. The goal of this study was to see whether a relationship could be found between maxacalcitol responsiveness and parathyroid gland size. METHODS: Parathyroid gland size was measured by ultrasonography in 25 patients with secondary hyperparathyroidism [serum intact parathyroid hormone (PTH) >300 pg/ml, 58.1 +/- 2.8 years old, 15 males and 10 females], who were treated with maxacalcitol. Patients were divided into two groups according to the mean value of the maximum diameter of the glands: group S with a diameter <11.0 mm and group L with a diameter >or =11.0 mm. Between the two groups there were no significant differences in serum intact PTH, calcium or phosphate level or duration of haemodialysis. RESULTS: Mean (+/- SE) maximal diameter of detectable parathyroid glands was 11.0 +/- 0.7 mm before treatment. At 4-24 weeks after administration of maxacalcitol, intact PTH concentrations decreased significantly in group S (from 546 +/- 39 to 266 +/- 34 pg/ml at 24 weeks; P < 0.01), but did not significantly change in group L (from 481 +/- 39 to 403 +/- 49 pg/ml at 24 weeks). At 24 weeks after maxacalcitol administration, the number of detectable parathyroid glands was significantly decreased in group S (from 2.2 +/- 0.3 to 1.8 +/- 0.4; P < 0.05), but not in group L. Serum calcium increased significantly in group L (from 9.6 +/- 0.2 to 10.2 +/- 0.3 mg/dl; P < 0.05), but not in group S. There was a significant correlation between reduction in PTH and parathyroid gland size (r = -0.42, P < 0.05). CONCLUSIONS: These results indicate that the responsiveness to maxacalcitol therapy of secondary hyperparathyroidism is dependent on parathyroid gland size and that the simple measurement of maximum parathyroid gland diameter by ultrasonography may be useful for predicting responsiveness to maxacalcitol treatment.  相似文献   

17.
The undetectable supernumerary and ectopic parathyroid glands have a high risk of persistent and recurrent hyperparathyroidism, especially in the patients with secondary hyperparathyroidism. Preoperative image diagnosis, CT scan, echogram and 201T1C1 scintigram were very useful for detecting supernumerary and ectopic parathyroid glands in our 132 patients who underwent parathyroidectomy for secondary hyperparathyroidism. Among these methods the scintigraphy showed the highest detection rate of the glands in the thymic tongue and in the upper mediastinum. CT scan showed the best detection rate of the glands located in the thyroid gland and those located between the thyroid gland and trachea. The echography was useful in detecting the glands in the thyroid gland, but could not offer easy visualization those located in the mediastinum. Even the ectopic parathyroid glands, weighing more than 500 mg were identifiable at about 90% when all the methods were applied routinely. In our experience, four patients had a supernumerary gland which was detected by the preoperative image diagnostic procedures at the initial surgery. One patient had a supernumerary gland in the mediastinum which was detected by image diagnosis after the initial operation and was removed at reoperation.  相似文献   

18.
Percutaneous catheter drainage offers an attractive alternative to open surgical drainage as the first choice in the treatment of retroperitoneal abscess. However, multiloculated abscess is difficult to drain percutaneously. We report a case of multiloculated retroperitoneal abscess successfully treated by percutaneous drainage with a Malecot catheter. A 47-year-old woman complained of fever and left flank pain. The peripheral while blood cell count was 16,800/mm3 and the blood sugar was 369 mg/dl. The computer tomographic (CT) scan showed a large multiloculated mass in the left retroperitoneum. An aspiration needle was inserted into the perinephric mass under ultrasonographic guidance. The definitive diagnosis of abscess was made by aspiration of purulent fluid. A 20 Fr. Malecot catheter was passed over the guide wire under fluoroscopic guidance. Two hundred ml of pus was smoothly aspirated. Streptococcus agalactiae was isolated from the aspirate. Antibiotics and insulin were started. The catheter was retained for 49 days until ultrasonography revealed disappearance of the abscess. One year later, she had no symptoms of recurrence.  相似文献   

19.
We report a case of composite pheochromocytoma-ganglioneuroblastoma in the adrenal gland with primary hyperparathyrodisim. A 55-year-old woman consulted our hospital for an examination of a right adrenal tumor, incidentally found by screening abdominal ultrasound sonography. On the clinical diagnosis of pheochromocytoma in the right adrenal gland from the findings of enhanced abdominal computed tomography, endocrinal examinations and 123I-metaiodobenzyl-guanidine scintigram, right adrenalectomy was performed transperitoneally. Histopathological diagnosis was an adrenal composite pheochromocytoma-ganglioneuroblastoma. This combination of compound adrenal tumor is extremely rare, and to date this case may be the seventh reported in Japan. Moreover, since her serum calcium level and intact parathyroid hormone level were high, so we considered the existence of multiple endocrine neoplasia type 2A. 99mTc-methoxyisobutylisonitrile scintigram and ultrasound of the neck revealed hyperparathyroidism, but medullary thyroid carcinoma was not detected. One year later, she was readmitted for parathyroid tumor excision, and histopathological finding was parathyroid adenoma. We concluded that she had both adrenal composite pheochromocytoma and hyperparathyroidism incidentally.  相似文献   

20.

Background

Endoscopic band ligation and glue injection are established techniques for variceal bleeding. As EUS may enhance variceal detection and improve therapeutic targeting, we aim to report our experience on EUS-guided coil embolization, with and without concomitant glue injection, of varices.

Methods

A prospectively maintained EUS database was retrospectively reviewed to identify consecutive patients who underwent EUS-guided variceal angiotherapy. All patients had failed or were poor candidates for standard endoscopic, surgical, or interventional radiologic therapies. The main outcome measurements were rates of rebleeding and adverse events.

Results

Fourteen patients [mean age 58 (SD 12) years, 50 % male] underwent EUS-guided coil injection with (n = 4) or without (n = 10) concomitant glue injection to treat esophagogastric (n = 1), gastric (n = 5), duodenal (n = 3), or choledochal (n = 5) varices. Prior endoscopic and cross-sectional imaging detected only 57 and 64 % of the varices seen. A mean of 5.1 (SD 1.9) coils and a median of 3.25 (range 2–3.5) mL of cyanoacrylate were injected during the initial procedure. During median follow-up of 12 (range 1–104) months, three patients died from unrelated causes and eight patients did not have further bleeding episodes. In the remaining three patients who had choledochal varices, the frequency and intensity of rebleeding decreased significantly. Only one asymptomatic adverse event occurred with coil migration to the liver.

Conclusions

EUS-guided angiotherapy of varices is safe and feasible in selected patients who failed conventional therapy, and should be considered in the clinical management of these patients.
  相似文献   

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