Selective Percutaneous Ethanol Injection Therapy Research Articles

Changes in Interventional Treatment—from the Viewpoint of Percutaneous Ethanol Injection Therapy

The environment surrounding secondary hyperparathyroidism treatment has changed and the transition of the guidelines on selective percutaneous ethanol injection therapy (PEIT) for secondary hyperparathyroidism from 2000 to 2006 has been made. The new guidelines emphasize the point that PEIT is best indicated for patients with one enlarged gland. Among treatments, including local vitamin D injection, selective PEIT and parathyroidectomy, cinacalcet is a potent medical treatment and will be a very effective new post-treatment intervention. However, it is expected that some patients will require active intervention based on morphological examination even if biochemical control is possible with cinacalcet administration.

Control of severe hyperparathyroidism in dialysis patients with nodular hyperplasia.

Secondary hyperparathyroidism is one of the most important abnormalities in chronic kidney disease-mineral and bone disorder (CKD-MBD). Despite the recent development of therapeutic modalities including new phosphate binders, new vitamin D analogues and cinacalcet, manypatientswithveryseverehyperparathyroidismstillremainuncontrollable.Severalstudieshavedemonstratedthat such refractory patients have markedly enlarged parathyroid glands with nodular hyperplasia composed of cells with decreased numbers of vitamin D and calcium-sensing receptors [1]. Percutaneous ethanol injection therapy (PEIT) of parathyroid glands was originally developed as an alternative to conventional surgical parathyroidectomy in Europe during the 1980s. Together with the advances in imaging techniques allowing identification of the glands to be destroyed, this therapy became a more sophisticated and practical therapeutic modality to control severe hyperparathyroidism during the early 1990s in Japan [2]. In this ‘selective PEIT’, glands with nodular hyperplasia are destroyed by ethanol injection, and remaining glands with diffuse hyperplasia are controlled by subsequent medical therapy. Analysis of the prognosis of parathyroid function following these procedures clearly suggests that patients with one nodular gland were best suited to selective PEIT [3]. The Japanese Society for Parathyroid Intervention, originally named as the Japanese Society for PEIT of Parathyroid, was established in 1996. The initial purpose of this society was to standardize the indication and protocol of PEIT. As a result, we published clinical guidelines for

Medical management after parathyroid intervention.

Vitamin D or vitamin D analogues pulse therapy is seldom effective in patients with at least one parathyroid gland with nodular hyperplasia, and surgical parathyroidectomy or parathyroid intervention is indicated. In parathyroid interventions, especially in selective percutaneous ethanol injection therapy (PEIT), the enlarged parathyroid gland(s) with nodular hyperplasia is selectively destroyed by ethanol injection, while other glands with diffuse hyperplasia are managed by medical therapy. Thus, medical management, e.g., use of appropriate dose of vitamin D or vitamin D analogues after the PEIT procedure, is as important as the destruction of the hyperplastic tissue itself. Recent studies showed that the combination of PEIT and intravenous vitamin D pulse therapy lead to reduce serum PTH level and calcium-phosphorus products in haemodialysis patients. In this article, we focus on the importance of medical therapy after PEIT, and review the efficacy of the combination of PEIT and intravenous vitamin D pulse therapy for haemodialysis patients with secondary hyperparathyroidism.

Pathophysiology of parathyroid hyperplasia in chronic kidney disease: preclinical and clinical basis for parathyroid intervention.

Secondary hyperparathyroidism is characterised by excessive secretion of parathyroid hormone and parathyroid hyperplasia, resulting in both skeletal and extraskeletal consequences. Recent basic and clinical studies have brought considerable advances in our understanding of the pathophysiology of parathyroid hyperplasia and have also provided practical therapeutic approaches, especially with regard to indications for parathyroid intervention. In this context, it is quite important to recognize the development of nodular hyperplasia, because the cells in nodular hyperplasia are usually resistant to calcitriol treatment. Patients with nodular hyperplasia should undergo parathyroid intervention including percutaneous ethanol injection therapy (PEIT). Selective PEIT of the parathyroid gland is an effective approach in which the enlarged parathyroid gland with nodular hyperplasia is ‘selectively’ destroyed by ethanol injection, and other glands with diffuse hyperplasia are then managed by medical therapy. With a more focused attention to applying parathyroid intervention, we can expect significant improvement in the management of secondary hyperparathyroidism in dialysis patients.

Combination Therapy of Intravenous Maxacalcitol and Percutaneous Ethanol Injection Therapy Lowers Serum Parathyroid Hormone Level and Calcium × Phosphorus Product in Secondary Hyperparathyroidism

Background: Percutaneous ethanol injection therapy (PEIT) is an alternative treatment for secondary hyperparathyroidism (SHPT). Although maxacalcitol has been recently developed as a new vitamin D₃ and its efficacy is anticipated in SHPT, there are only few reports on the usefulness of combination therapy of intravenous maxacalcitol and selective PEIT. Methods: The study population comprised 10 hemodialysis patients (6 males and 4 females, mean age; 51.5 ± 13.5 years, mean HD period 13.7± 3.5 years), with high intact-PTH level (>400 pg/ml) and 1 or 2 enlarged parathyroid glands detected by power Doppler ultrasonography. Intravenous maxacalcitol therapy commenced one week after PEIT at 15 µg/week. The effect of combination therapy was monitored by measuring intact-PTH, serum Ca and P, bone metabolic markers, parathyroid gland volume and bone mineral density, prior to and at 6 and 12 months after PEIT. Results: Successful control of intact-PTH, bone metabolic markers and parathyroid gland volume was achieved using the combination therapy. Serum P and Ca×P productweresignificantly decreased 12 months after PEIT. The mean values of serum intact-PTH, P and Ca×P product fulfilled all of the K/DOQI guidelines at 12 months after PEIT. None of the patients developed complications related to PEIT-maxacalcitol therapy during 12 months following PEIT. Conclusion: Combination therapy of intravenous maxacalcitol therapy and selective PEIT is safe and effective for the treatment of refractory SHPT. This combination therapy results in suppression of PTH secretion, regression of parathyroid hyperplasia and the control of Ca×P product, which may prevent calcific uremic arteriolopathy in dialysis patients.

Surgical verification of percutaneous maxacalcitol injection therapy on enlarged parathyroid glands in chronic dialysis patients.

Selective percutaneous ethanol injection therapy (PEIT) has been used to control parathyroid function in patients with secondary hyperparathyroidism (2HPT) when one or more parathyroid gland (PTG) progresses to the nodular hyperplasia stage. However, PEIT can have adverse side effects, such as nerve paralysis and adhesion, because the ethanol is destructive. Intraparathyroid injection of a vitamin D analogue has been designed as a treatment to control parathyroid function without destruction of the PTG or causing adhesions to the surrounding tissue, and the present study aimed to verify the effect of percutaneous maxacalcitol (22-oxacalcitriol) as the vitamin D analogue. The study group comprised two haemodialysis patients who needed parathyroidectomy for uncontrolled 2HPT with a maximal PTG diameter >20 mm. The treatment began with an ultrasonographically guided injection of 10 microg of maxacalcitol solution into the largest PTG and, 1 week later, parathyroidectomy was performed to examine the effect of the maxacalcitol injection both macroscopically and microscopically. The injected glands were swollen and inflamed, and adhesions made it difficult to remove them. There was macroscopic and microscopic evidence of haemorrhagic necrosis and adhesions to the surrounding tissue. Direct vitamin D analogue injection should not be performed as a primary treatment option because the adverse side effects are not overcome by this technique.

Efficacy of direct injection of calcitriol into the parathyroid glands in uraemic patients with moderate to severe secondary hyperparathyroidism.

Secondary hyperparathyroidism (2HPT) is a common complication in uraemic patients. When medical therapy, including high doses of intravenous calcitriol, fails to suppress the pathological secretion of parathyroid hormone (PTH), one of the newly developed interventional techniques, such as percutaneous ethanol injection therapy (PEIT), is an option before taking the surgical solution. A protocol for direct calcitriol injection therapy and a discussion of its effectiveness and limitations for an enlarged parathyroid gland(s) are presented. Nine patients were selected according to the Japanese Guideline for Selective PEIT. Using the same technique as PEIT, a dose of calcitriol that was approximately 200-300% of the calculated volume of the selected parathyroid gland was injected directly into the gland under ultrasonographic guidance. In six cases, the intact PTH concentration decreased to <360 pg/ml. The total volume of the enlarged parathyroid gland(s) also decreased to 54.7% of the initial volume. The blood supply to the treated glands, as evaluated by colour Doppler imaging, appeared to diminish transiently after injection, probably from the volume effect of this procedure. The number of enlarged parathyroid glands was not a limiting factor for this therapy; however, a grossly enlarged parathyroid gland (>2000 mm(3)) appeared to be resistant to this intervention and an intrathoracic parathyroid gland was found in a non-responsive case. None of the patients had any severe complications, such as nerve palsy or massive haemorrhage. This new approach to the control of 2HPT is recommended as an alternative pharmacological parathyroidectomy to surgical therapy.

Renoprotection following Treatment of Secondary Hyperparathyroidism with Percutaneous Ethanol Injection in Pre-Dialysis Patients

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 µg 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.

Long-term prognosis of parathyroid function after successful percutaneous ethanol injection therapy (PEIT) guided by color Doppler flow mapping in chronic dialysis patients

Secondary hyperparathyroidism (2 HPT) is a representative disease of dialysis osteopathy, with the lesion that makes fibrous osteitis and the parathyroid hyperplasia by the hyper secretion of parathyroid hormone (PTH). This research examines the usefulness of selective percutaneous ethanol injection therapy (PEIT) of parathyroid glands in order to treat and control for 2 HPT. PEIT was performed in 46 patients resistant to calcitriol pulse therapy and all glands larger than 5 mm in diameter were destroyed by ethanol guided by power Doppler flow mapping. Serum intact-PTH (iPTH) levels fell from 633.3 +/- 359.9 to 226.3 +/- 204.7 pg/mL at three weeks and were maintained at 289.9 +/- 222.4 pg/mL at one year after PEIT. Total alkaline phosphatase activity fell from 384.9 +/- 160.1 to 234.0 +/- 110.5 IU/L at one year after PEIT. In 19 patients, i-PTH levels fell into relative hypoparathyroidism (iPTH < 160 pg/mL) at three weeks after PEIT: however, they recovered at one year after PEIT (191.1 +/- 29.6 pg/mL). In total, parathyroid function was maintained at optimal range (160 < iPTH < 360 pg/mL) in 80.4% of patients at one year after PEIT with appropriate medical therapy. As for the complications, recurrent nerve palsy was observed in only one patient, but was reversible. In conclusion, selective PEIT appears to be able to control appropriate parathyroid function and to be the method of choice to treat 2 HPT prior to parathyroidectomy.

Management of renal hyperparathyroidism

Histopathological and pathophysiological investigations including the genetic approach have been contributing to management of renal hyperparathyroidism (HPT). In renal failure, parathyroid glands initially proliferate diffusely and polyclonally, and then are transformed to monoclonal nodular hyperplasia with aggressive growth potential and diminished expression of both the vitamin D receptor and calcium-sensing receptor. When more than one parathyroid gland progresses to nodular hyperplasia, HPT is refractory to medical treatment. To prevent advanced renal HPT, progression to nodular hyperplasia should be avoided. Control of hyperphosphatemia is very important to prevent advanced renal HPT, but it is usually difficult. Administration of vitamin D metabolites constitutes the most promising form of prophylaxis and should be performed with monitoring of the PTH level to avoid adynamic bone disease. Calcitriol pulse therapy is effective for advanced renal HPT; however, when parathyroid glands progress to nodular hyperplasia, surgical treatment should be considered. Measuring parathyroid volume by ultrasonography is useful for detecting nodular glands and deciding treatment options. Parathyroidectomy (PTx) is an effective treatment for advanced renal HPT. However, the timing of the operation is important, because the improvement of skeletal deformity and vessel calcification inducing high mortality risk cannot be expected even after successful surgery. Total PTx with forearm autograft is a suitable procedure for renal HPT. Recently. selective percutaneous ethanol injection therapy has been adopted as an alternative treatment to PTx, and new vitamin D analogues, phosphate binders without calcium, and calcimimetics have been developed as new options for management of renal HPT.

Medical and surgical aspects of parathyroidectomy

A more logical approach to the management of the chronic dialysis patient with parathyroid hyperplasia has become possible thanks to recent progress in cellular and molecular analysis of surgically removed parathyroid glands and accumulation of clinical experience. When one or more parathyroid glands progress to the stage of nodular hyperplasia, it is usually difficult to control PTH secretion even by calcitriol pulse therapy. For such patients, we have developed two new therapeutic approaches, i.e., selective percutaneous ethanol injection therapy (PEIT) and direct calcitriol injection therapy, in combination with medical therapy. For optimal selection of therapeutic modalities it is indispensable to evaluate the degree and stage of parathyroid hyperplasia. For successful management, prevention of nodular hyperplasia is the most important strategy.

Selective percutaneous ethanol injection therapy (PEIT) of the parathyroid in chronic dialysis patients—the Japanese strategy

Selective percutaneous ethanol injection therapy (PEIT) of the parathyroid in chronic dialysis patients—the Japanese strategy

Prognosis of parathyroid function after successful percutaneous ethanol injection therapy guided by color Doppler flow mapping in chronic dialysis patients.

Selective percutaneous ethanol injection therapy (PEIT) of the parathyroid glands has been shown to be effective in chronic dialysis patients with severe secondary hyperparathyroidism. In this study, we examined whether it was possible to maintain parathyroid function within target range (intact parathyroid hormone [iPTH], 160 to 360 pg/mL) in the long term after successful destruction of hyperplastic tissue. PEIT was performed in 46 patients resistant to calcitriol pulse therapy, and all glands larger than 5 mm in diameter were destroyed by ethanol, guided by power Doppler flow mapping. Serum iPTH levels decreased from 633.3 +/- 359.9 to 226.3 +/- 204.7 pg/mL at 3 weeks and were maintained at 289.9 +/- 222.4 pg/mL at 1 year after PEIT. Total alkaline phosphatase activity decreased from 384.9 +/- 160.1 to 234.0 +/- 110.5 IU/L at 1 year after PEIT. In 19 patients, iPTH levels decreased into relative hypoparathyroidism (iPTH < 160 pg/mL) at 3 weeks after PEIT; however, they recovered at 1 year after PEIT (191.1 +/- 29.6 pg/mL). Parathyroid function was maintained within target range in 80.4% of the patients at 1 year after PEIT with appropriate medical therapy. Surgical parathyroidectomy was not required in any patient. Conversely, in eight other patients with recurrent hyperparathyroidism after subtotal parathyroidectomy, iPTH levels recovered in only 50% of the patients at 1 year after PEIT. Thus, destruction of hyperplastic tissue should be optimized in such patients. Recurrent nerve palsy was observed in only one patient, but was reversible. In conclusion, selective PEIT guided by color Doppler flow mapping is an effective and safe adjunct to medical therapy with a low risk for hypoparathyroidism.