Removal of autografted parathyroid tissue for recurrent renal hyperparathyroidism in hemodialysis patients.

BACKGROUND: Recurrent renal hyperparathyroidism (HPT) is a serious problem after parathyroidectomy (PTx). We evaluated the frequency of graft-dependent recurrent HPT and the clinical outcomes after removal of the autograft. METHODS: Between March 1980 and January 2009, 2660 patients underwent total PTx with forearm autograft. After resection of all parathyroid glands, 30 pieces of 1 x 1 x 3 mm parathyroid tissue from diffuse hyperplasia, if possible, were autografted into brachioradial muscle. Graft-dependent recurrence of HPT was diagnosed by a high PTH gradient and detection of swollen autografts by palpation and/or MRI or US. RESULTS: In 248/2660 (9.3%) patients, removal of the graft was required a total of 327 times (53 patients required removal of the autograft several times). The cumulative frequency of graft-dependent recurrent HPT was 17.4% ten years after the initial PTx. Thirty-two patients underwent both resection of missed glands located in the neck or mediastinum and removal of the graft. En-bloc resection of autograft with surrounding muscle was required to avoid reoperation. When the intact PTH level dropped under 300 pg/ml, in the majority of patients renal HPT could be medically managed after the operation. The mean weight of the resected parathyroid tissue was 1583.7 mg. No specimen had histopathologically malignant features. Three patients suffered from hematoma in the wound. CONCLUSIONS: Graft-dependent recurrent renal HPT is not negligible. However, in the majority of patients, renal HPT can be controlled by removal of the autograft noninvasively. Total PTx with forearm autograft is preferable for hemodialysis patients, especially when long-term survival is expected.

Surgical and medical treatment of secondary hyperparathyroidism in patients on continuous dialysis.

BACKGROUND: Secondary hyperparathyroidsm (2HPT) is a common complication in hemodialysis patients associated with morbidity and sometimes mortality. The majority of patients with 2HPT can be managed by medical treatment. However, medical treatment does not always provide control of parathyroid disorder. Some patients require surgical treatment, parathyroidectomy (PTx). Successful surgical treatment often results in dramatic drop of the parathyroid hormone (PTH) levels, relieves the patients from clinical symptoms, and reduces mortality. However, at present we do not have reliable evidences showing that PTx. METHODS: The published papers about medical and surgical treatment for 2HPT within the last 10 years were evaluated to acquire the evidence for the adequate surgical treatments for 2HPT. RESULTS: Many retrospective, observation studies have confirmed that successful PTx can achieve a dramatic drop of PTH levels, relieve symptoms of 2HPT and reduce mortality. However, we do not have reliable evidence that PTx compared with placebo or active drugs, improves mortality or outcome with respect to cardiovascular symptoms, bone disease, or biochemical parameter. The indications for surgery may be strongly influenced by medical therapy, including treatment with calcimimetics, as well as by composition of the patients material and medical insurance system. There are many treatment of modalities in addition to PTx for dialysis patients with 2HPT. Moreover, we do not have clear evidence telling us which operative procedures is most appropriate for 2HPT, with respect to clinical effectiveness, mortality or risk for recurrence. CONCLUSION: To acquire the evidence for the adequate medical and surgical treatment for 2HPT including operative procedures, randomized controlled prospective studies are requires.

Parathyroidectomy for secondary hyperparathyroidism in the era of calcimimetics.

Secondary hyperparathyroidism (SHPT) is one of the major complications experienced by patients with renal failure. Cinacalcet hydrochloride, a calcimimetic, is a new modality for the treatment of SHPT and is able to suppress a high parathyroid hormone level remarkably well. However, for patients with uncontrollable SHPT while on cinacalcet, those with severe SHPT symptoms and those with difficulty being treated with cinacalcet because of side-effects, parathyroidectomy (PTx) may be indicated as usual. PTx can induce a remarkable improvement in SHPT: postoperative serum phosphorus and calcium levels are easily maintained within their target ranges, quality of life is improved, survival rates are improved and the procedure has high cost-effectiveness, so for the patients with SHPT refractory to conventional vitamin D or vitamin D analog treatment in whom long-term survival is expected, PTx might be a more preferable treatment. On the other hand, cinacalcet is the first choice for patients in whom it is difficult to manage SHPT with PTx. Indications are patients (i) for whom surgery under general anesthesia would be highly invasive; (ii) whose parathyroid glands are located in an area making resection difficult; (iii) in whom the affected parathyroid tissues are difficult to identify; (iv) in whom it is difficult to resect all affected parathyroid tissues; and (v) who have undergone repeated surgery or percutaneous ethanol injection therapy and may develop serious complications such as bilateral recurrent laryngeal nerve paralysis. Cinacalcet may be a rescuer treatment for these patients.

Modified laparoscopic splenectomy: a beneficial technique for ABO-incompatible living donor renal transplantation candidates on hemodialysis.

Advances in laparoscopy have enabled minimally invasive surgical treatment of splenic diseases. Even with these advances, laparoscopic splenectomy in patients on dialysis can be difficult because of tissue fragility due to the underlying renal disease. We report a safe surgical technique for laparoscopic splenectomy in patients on maintenance dialysis that is suitable for use before ABO-incompatible living donor renal transplantation (LDRTx). Between June 1972 and December 2006, a total of 800 patients underwent LDRTx in our department, including 82 patients who underwent ABO-incompatible LDRTx. Between April 2001 and December 2006 we performed laparoscopic splenectomy in 48 hemodialysis patients as a pretreatment before ABO-incompatible LDRTx. Under general anesthesia the operation was performed using a new technique, referred to as the "splenic hilum lump method." We evaluated the surgical outcomes, such as the operative time, amount of blood loss, efficacy, and complications. The mean operative time was 131.6 +/- 38.4 min and mean blood loss was 126 +/- 395 mL. Blood transfusion was required in three patients. All cases had satisfactory kidney function after LDRTx and none developed kidney graft failure due to acute rejection. Almost all patients could walk the day after laparoscopic splenectomy and were satisfied with the cosmetic appearance of the scar after wound healing. The surgical technique we report here can be safely performed on patients with renal failure who require caution because of tissue fragility. Laparoscopic splenectomy is a safe, effective and less invasive operative procedure as a pretreatment for ABO-incompatible LDRTx.

Relationship between the dimension of parathyroid glands estimated by ultrasonography and the hyperplastic pattern in patients with renal hyperparathyroidism.

In renal hyperparathyroidism (HPT), the parathyroid glands initially proliferate diffusely and polyclonally, and are then transformed to monoclonal nodular hyperplasia with aggressive growth potential. In this study we evaluated the relationship between the maximal dimension of parathyroid glands estimated by ultrasonography (US) and the hyperplastic pattern of parathyroid glands in patients with renal HPT. Between October 1999 and December 2006, 141 patients who underwent total parathyroidectomy (PTx) with forearm autograft in our department were enrolled in this study. In these patients 308 parathyroid glands were detected by US before PTx. The largest dimension of the gland estimated preoperatively by US was correlated closely with its measurement at surgery (R2 was 0.31, P < 0.001). The maximal dimension of diffuse hyperplastic glands was significantly smaller than that of the glands with nodular hyperplastic glands (P < 0.001). There was a strong correlation between the pattern of parathyroid hyperplasia and the glandular diameter when we defined 8 mm as the maximal diameter estimated by US as a cut-off value. As a result of receiver operating characteristic analyses, using these criteria the US technique could predict nodular hyperplasia with a high sensitivity (78.9%) and specificity (78.7%). Parathyroid glands that are enlarged by more than 8 mm in the largest dimension estimated by US may represent glands with nodular hyperplasia.

Incidence of parathyroid glands located in thymus in patients with renal hyperparathyroidism.

BACKGROUND: Parathyroid glands are frequently located in thymus, and it is essential to resect thymic tissue from the neck incision, especially in surgery for renal hyperparathyroidism (HPT). METHODS: In this study, we evaluated the incidence, location, and type of intrathymic parathyroid glands in 902 patients who underwent initial parathyroidectomy (PTx) for advanced renal HPT in our department. Removal of the thymic tongues on both sides was routinely performed from the neck incision, and the thymic tissue was carefully examined both macroscopically and microscopically. RESULTS: Of the 902 patients in the study, 269 had only inferior parathyroid glands in the thymus, in 62 patients only supernumerary glands were found in the thymic tongue, and in 78 patients both inferior and supernumerary glands were present in thymic tissue. Therefore the incidence of patients with intrathymic glands was 45.3% (269 + 62 + 78 = 409/902). In 129 (92.1%) of 140 patients with supernumerary glands in the thymic tongue, these glands were detected only on histopathological examination, and about half of them were classified as the parathyromatosis type. CONCLUSIONS: In the human, parathyroid glands might be located in the thymus in about 50%. If the inferior gland/glands cannot be found around the inferior pole of thyroid lobe, it is very important to search for glands in the thymic tongue. Moreover, to avoid missing supernumerary glands, removal of the thymic tongue on both sides is essential in surgery for renal HPT.

Expression of parafibromin in distant metastatic parathyroid tumors in patients with advanced secondary hyperparathyroidism due to chronic kidney disease.

BACKGROUND: Recently, somatic inactivating mutations in HRPT2 have been reported in the majority of sporadic parathyroid carcinoma in primary hyperparathyroidism (HPT). Parafibromin is a tumor suppressor protein encoded by HRPT2, and loss of nuclear expression of parafibromin was found in approximately 70% of the carcinoma. In secondary HPT due to chronic kidney disease (CKD), parathyroid carcinoma is very rare and whether HRPT2 plays a role in the carcinogenesis in these cases is not clear. We evaluated the expression of parafibromin in hemodialysis patients with distant metastatic parathyroid tumors. METHODS: Between June 1973 and December 2006, 2,142 patients underwent parathyroidectomy (PTx) for secondary HPT in our department. We encountered five (0.23%) patients with distant metastatic parathyroid tumors. We evaluated the immunohistochemistry for parafibromin in eight primary parathyroid glands removed from the neck at the initial operation and/or at reoperation and seven distant metastatic tumors resected at reoperation. RESULTS: In only one lung metastatic parathyroid tumor, negative staining for parafibromin was detected. In the other three lung, two regional node, and one chest wall metastatic parathyroid tumor, parafibromin was strongly stained in the nuclei of the parathyroid cells. Among eight primary glands, except for one with weakly positive staining, the expression of parafibromin was detected diffusely and strongly. CONCLUSION: We conclude that the inactivating mutations and/or allelic loss of the HRPT2 gene may not play a major role in parathyroid carcinogenesis in secondary HPT due to CKD, but in these cases cancer development may be associated with a heterogeneous genetic disorder.

QuiCk-IntraOperative Bio-Intact PTH assay at parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: In uremic patients, metabolism of 1-84 parathyroid hormone (PTH) and fragments are delayed, and in these patients, the usefulness of intraoperative PTH assay may be problematic. We evaluated the usefulness of the QuiCk-IntraOperative Bio-Intact PTH (QPTH) assay for uremic patients with secondary hyperparathyroidism who required total parathyroidectomy (PTx) with forearm autograft. The purpose of our study was to recognize whether QPTH in uremic patients was useful to determine during operation whether complete PTx had been achieved. METHODS: Forty-four patients who underwent initial PTx were enrolled in this study. Blood samples were drawn just after induction of general anesthesia (basal samples), immediately after removal of the last gland, and at 5, 10, 15, and 30 minutes, and at the first morning after PTx. The assay was performed immediately after sample collection. Reductions of PTH levels were evaluated and expressed in percentage of basal levels. RESULTS: The mean PTH levels in 41 patients, excluding 3 in whom the PTH level did not drop significantly (>60 pg/ml), measured by QPTH at anesthesia, 0, 5, 10, 15, and 30 minutes were 734.3, 104.7, 58.8, 37.4, 27.0, 16.3 pg/ml, corresponding to 100%, 17.1%, 9.3%, 5.8%, 4.1%, 2.4% of the preexcision values, respectively. If the cutoff value was defined as 10.8% at 10 minutes, the sensitivity was 100% and specificity 90%. When the QPTH level dropped to under 10.8% at 10 minutes, we could consider that all glands were removed. CONCLUSIONS: QPTH in uremic patients is very useful to determine whether complete PTx is achieved during operation.

Recurrent renal hyperparathyroidism caused by parathyromatosis.

BACKGROUND: Parathyromatosis is defined as multiple foci of benign hyperfunctioning parathyroid tissue in the neck or mediastinum. Parathyromatosis is a problematic cause of recurrent hyperparathyroidism (HPT). In renal HPT, the stimuli of the parathyroid cells persist after parathyroidectomy (PTx), and for this reason, parathyromatosis might be important in renal HPT. METHODS: Between July 1973 and December 2005, 1,932 patients underwent PTx for advanced renal HPT in our department. We evaluated the frequency, clinical findings and the prognosis of this kind of parathyroid disorder. RESULTS: After total PTx with forearm autograft for renal HPT, which was performed initially in our department, the risk for developing parathyromatosis was 0.11% (2/1837); after sub-total PTx, it was 5% (1/20). The risk for developing parathyromatosis was lower after total PTx with forearm autograft than after sub-total PTx (P < 0.05). In patients who developed persistent or recurrent HPT and were referred to our department for neck re-operation, parathyromatosis occurred in 12.1% (7/58); in those originally operated on at our hospital, the corresponding figure was 7.1% (3/42). This difference was not significant (P = 0.42). Only in 4 of 10 patients was parathyromatosis suggested before re-operation. However, in spite of several re-operations, high parathyroid hormone (PTH) levels persisted in 6 of 10 patients with parathyromatosis. CONCLUSION: Parathyromatosis is a non-negligible cause of recurrent renal HPT in patients who require neck re-exploration. Parathyromatosis is difficult to diagnose pre-operatively and completely controlled by re-operation. Parathyromatosis should be kept in mind when performing neck re-exploration for recurrent renal HPT.

Surgical significance of undescended parathyroid gland in renal hyperparathyroidism.

BACKGROUND: In renal hyperparathyroidism, in which basically all parathyroid glands are hyperplastic, overlooking one undescended parathyroid gland becomes important. METHODS: Between July 1973 and December 2004, 1750 patients in our department underwent parathyroidectomy for severely advanced renal hyperparathyroidism. We evaluated the frequency and location of undescended parathyroid glands and the clinical findings and the prognosis of patients with such glands. RESULTS: Undescended parathyroid glands in our series of renal hyperparathyroidism numbered 16 of 1750 cases (0.91%). In 9 patients, the glands were removed at the initial parathyroidectomy in our hospital. Two of these glands were detected by preoperative imaging; 6 glands were removed with an undescended thymus. The mean weight of the undescended parathyroid glands that were removed at initial operations was 470 mg (30 to 1392 mg). In 7 other patients, unrecognized undescended glands were responsible for persistent hyperparathyroidism in 6 patients and recurrent disease in 1 patient. In 4 of these 7 patients, the initial parathyroidectomy was performed at our hospital; in the other 3 patients, the initial parathyroidectomy had been done at another hospital, and the glands were removed on reoperation. The mean weight of these glands was 1295 mg (range, 444-2396 mg). In 12 of a total of 16 patients with undescended glands, there appeared to be an inferior parathyroid gland, and the other 4 glands appeared to be a superior gland. No glands were detected by sestamibi scans. CONCLUSION: In operations for renal hyperparathyroidism, an undescended parathyroid gland can be readily overlooked, which leads to persistent or recurrent hyperparathyroidism. Because an undescended parathyroid gland is not always an inferior gland, in surgery for persistent and/or recurrent renal hyperparathyroidism, it is very important to examine carefully the submandibular portion to detect such an undescended gland.

[Two patients with hyperparathyroidism which was progressive for more than ten years after successful kidney transplantation].

It is well known that in some patients advanced renal hyperparathyroidism (HPT) persists after successful kidney transplantation (RTx) and in those patients parathyroidectomy is required usually within one year after RTx. We experienced two patients with advanced renal HPT which released after successful RTx and parathyroidectomy was performed in more than 10 years after RTx, even their kidney function was well-preserved. Hypercalcemia was gradually progressive for ten years after RTx and enlarged parathyroid glands were detected by image diagnosis. We performed parathyroidectomy and HPT was dramatically improved. It is possible that primary HPT occurred de novo after RTx or renal HPT was progressive. We evaluated those possibility based on histopathological findings dramatically improved of removed parathyroid glands.

Calciphylaxis: a rare complication of patients who required parathyroidectomy for advanced renal hyperparathyroidism.

Calciphylaxis is a relatively rare but life-threatening complication in uremic patients. Clinical findings and prognosis were evaluated in six patients who developed calciphylaxis from a group of 1499 patients who underwent parathyroidectomy (PTx) for advanced renal hyperparathyroidism (HPT) in our department from July 1972 to July 2003. The frequency of calciphylaxis was 0.40% (6/1499). Two patients were women and four were men. The mean age was 50.5 years, and the mean duration of hemodialysis (HD) treatment was 14.0 years. In five of six patients, calciphylaxis was classified as distal type; in one case, as proximal type. In three patients, calciphylaxis was diagnosed at the time for PTx. In two patients, calciphylaxis was identified after PTx, although the serum parathyroid hormone (PTH) level was within the appropriate range for dialysis patients. In two patients, calciphylaxis improved after PTx, but two patients required leg and toe amputations after PTx. In one patient with the proximal type of calciphylaxis, the condition occurred when a high PTH level recurred after the initial PTx. The patient died as a result of a serious infection due to uncontrollable skin ulcers. Calciphylaxis is a rare complication in patients who require PTx for renal HPT. Especially the proximal type has a poor prognosis. High levels of the Ca x P product and/or PTH are risk factors. Therefore, this syndrome should be kept in mind and attention should be paid to reduce risk factors. It is important that PTx being performed at the right time in patients with advanced renal HPT refractory to medical treatment.