Parathyroid autotransplantation: an update

APPENDIX. (continued) Scoring System

Description*

SF-36 (Medical Outcomes Study Short Form Survey)

Thirty-six self-administered questions that assess 8 concepts: functioning (physical and social), role (physical and emotional), mental health, pain, vitality, and general health perception. A score of 0 to 100 is calculated for each of 8 scales. Higher scores indicate a better quality of life. WHO (World Health Organization) Five questions that score performance as Performance Score follows: 0 Normal 1 Unable to perform strenuous activity 2 Ambulatory, but cannot work 3 Confined to bed/chair with limited selfcare 4 Completely disabled; no self-care. * Descriptions are taken from the articles cited in this cluster.

Endocrine Parathyroid Autotransplantation: An Update Guest Reviewers: D. Kirkland Rawl, MD, and Joseph B. Cofer, MD REVIEWER COMMENTS

Traditionally, parathyroid tissue has been autotransplanted into muscle. Common locations include the muscles of the forearm and the sternocleidomastoid muscle. This article discussed 59 patients with hyperparathyroidism associated with renal failure in which parathyroid tissue was autotransplanted into presternal subcutaneous fat, as opposed to muscle. The incidence of persistent postoperative hypoparathyroidism was 14%, slightly higher than typically reported. Twelve percent required reoperation with partial excision of the autograft for recurrent parathyroid hyperplasia. Overall, only 71% of patients had an optimal outcome with only 1 operation.

LONG-TERM RESULTS OF SUBCUTANEOUS PARATHYRIOD GRAFTS IN UREMIC PATIENTS. Kinnaert P, Salmon I, Decoster-Gervy C, et al. Arch Surg 2000;135:186-190. Objective: To evaluate the late results of total parathyroidectomy and subcutaneous

implantation of autologous parathyroid tissue in the treatment of secondary hyperparathyroidism. The authors hypothesized that their results were at least as good as those reported for intramuscular grafting. Design: The study is a retrospective analysis. Failure of treatment, recurrence of disease, and hypoparathyroidism were the main outcomes measured. The authors also evaluated the rate of recurrent hyperparathyroidism when grafting diffuse versus nodular type glandular hyperplasia. Intact parathyroid hormone (PTH) levels were measured using an immunoradiometric assay. Hypoparathyroidism was defined as an intact PTH level below 1.6 pmol/liters (normal range 1.6 to 5.8 pmol/liters) with a normal or low blood calcium level. Hyperparathyroidism was defined as PTH greater than 5.8 pmol/liters. Setting: A university hospital and 9 affiliated dialysis units in Brussels, Belgium. Participants: Fifty-nine patients (33 women and 26 men) with hyperparathyroid-

ism associated with renal failure who had failed medical management were selected for the surgical group. They underwent total parathyroidectomy with subcutaneous autografting anterior to the lower third of the sternum. Patients were selected between November 1986 and August 1996 and were observed for 12 to 130 months (median 38 months). No patient was lost to follow-up. Patients with concomitant diseases that CURRENT SURGERY • Volume 58/Number 1 • January/February 2001

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interfere with calcium and phosphorus metabolism were excluded. No patients were diabetic. Comparisons were made to historical controls and a population of 90 hemodialysis-dependent patients with no indication for surgical therapy. Results: Fifty-nine patients were included in the surgical series. Four glands were

removed in all but 2 patients, in whom five glands were found. A total of 9 patients (15%) underwent a second surgery. Two patients (3%) required re-exploration for supernumerary glands and 7 patients (12%) required excision of grafted tissue for recurrent hyperparathyroidism 15 to 108 months (median 39 months) after the first operation. Four of the 50 patients who did not require a second surgery received a kidney transplant. Two of the transplant patients had intact PTH levels in the normal range and two had levels exceeding 5.8 pmol/liters. Forty-six patients remained on hemodialysis and had the following intact PTH levels: 8 patients below 1.6 pmol/liters, 16 in the normal range, and 22 greater than 5.8 pmol/liters. All patients received cholecalciferol, oral calcium, or both, and their blood calcium levels were maintained within the normal range. Histologic evaluation of grafted tissue was available in 48 patients. Twenty-two patients were grafted with tissue containing nodular-type hypertrophy. There was no difference in the rate of recurrent hyperparathyroidism between those grafted with diffuse-type hypertrophy and those grafted with nodular type. In patients not requiring excision, the mean intact PTH level was higher in those grafted with nodular tissue (12.8 ⫾ 2.5 pmol/liters) than in those grafted with only diffusetype hypertrophy (7.4 ⫾ 1.4 pmol/liters). This difference did not reach statistical significance. Conclusions: The late results of total parathyroidectomy and presternal subcutane-

ous grafting compare favorably with published data on other surgical techniques proposed for the treatment of renal hyperparathyroidism. The ease with which the hypertrophied grafts are removed when the disease recurs warrants further use of this procedure.

PARATHYROID AUTOTRANSPLANTATION WITH TOTAL THYROIDECTOMY FOR THYROID CARCINOMA: LONG-TERM FOLLOW-UP OF GRAFTED PARATHYROID FUNCTION. Kikumori T, Imai T, Tanaka Y, et al. Surgery 1999;125:504-508. Objective: To evaluate the long-term function of parathyroid autotransplantation to the pectoralis major muscle following total thyroidectomy and bilateral neck dissection for thyroid cancer. Design: A retrospective analysis of a consecutive surgical series. Hypoparathyroidism

is defined as a condition that requires calcium or vitamin D supplementation to maintain normocalcemia and where the serum intact parathyroid hormone (PTH) level falls below the normal range (10 to 65 pg/ml). Setting: Department of Surgery II, Nagoya University School of Medicine, Nagoya,

Japan.

REVIEWER COMMENTS

This study supports preserving parathyroid glands in situ, when feasible, during total thyroidectomy. However, if the required cervical dissection threatens to devascularize the parathyroid glands, they can be sucessfully autotransplanted into the pectoralis major muscle 95% of the time. Transient postoperative hypoparathyroidism is expected after autotransplantation. The article also suggests that autotransplantation of at least 3 parathyroid glands is associated with the best outcome.

Participants: This study investigated 84 patients with thyroid carcinoma who un-

derwent total thyroidectomy, bilateral modified neck dissection, and total parathyoidectomy with autotransplantation of 2 or more glands. All autotransplanted glands were minced and grafted within the pectoralis major muscle. Twenty patients with incidentally discovered thyroid carcinomas underwent only total thyroidectomy for presumed benign disease and served as a control group. Parathyroid glands in the control group were left in situ. Patients whose serum intact PTH, calcium, and phosphorus levels were measured for more than 1 year were eligible. One patient who required reoperation and those patients lost to follow-up within 1 year were excluded from the study. The mean follow-up was 34 months. 16

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Results: The serum intact PTH level fell to below detectable levels in all 84 patients

who underwent parathyroid autotransplantation. Eighty (95%) of the intact PTH levels returned to the normal range within 1 month of surgery. Two of the patients with normal PTH levels required 1 ␮g of 1-␣ vitamin D3 to maintain normocalcemia. The 4 hypoparathyroid patients (5%) were normocalcemic with 2 ␮g of 1-␣ vitamin D3. No patient required oral calcium. No patient in the control group developed transient or permanent hypoparathyroidism. The average postoperative serum intact PTH concentration seemed to correlate with the number of autotransplanted glands but failed to reach statistical significance, except in patients with only 2 autotransplanted glands. Conclusions: The recovery patterns of the intact PTH concentration indicate that the glands were grafted successfully and functioned for a long period. This method of parathyroid autotransplantation is feasible, can be performed simply, and compares favorably to previous reports in terms of the incidence of permanent postoperative hypoparathyroidism. REVIEWER COMMENTS

This article discusses a series of patients undergoing thyroid surgery in which immediate autotransplantation was performed on all devascularized or inadvertently removed parathyroid glands. The authors demonstrated that frozen section confirmation of the presence of parathyroid tissue is unnecessary to prevent postoperative hypoparathyroidism if immediate autotransplantation is employed. The authors feel that immediate autotransplantation of devascularized glands has the advantage of improved graft survival and decreased operating time while avoiding the added cost of frozen section examination.

PARATHYROID AUTOTRANSPLANTATION DURING THYROIDECTOMY: IS FROZEN SECTION NECESSARY? Lo CY, Lam KY. Arch Surg 1999;134:258260. Objective: To evaluate the accuracy of parathyroid gland identification and the need for frozen section confirmation prior to autotransplantation during thyroidectomy. Design: A prospective case series. Setting: University of Hong Kong Medical Center, Queen Mary Hospital, Hong

Kong, China. Participants: The study is comprised of patients with devascularized or inadver-

tently removed parathyroid glands that were subsequently autotransplanted. All patients were undergoing thyroidectomy for a variety of benign and malignant thyroid diseases. One hundred fifty-two patients (a total of 179 attempted parathyroid autotransplantations) were entered into the study from January 1995 to December 1997. The suspected parathyroid gland was minced and immediately implanted into the ipsilateral sternocleidomastoid muscle. A portion of the tissue was sent for confirmation of its histologic identity. Routine frozen section examination was not performed. Results: One hundred sixty-seven (93.3%) of the 179 tissue samples were confirmed

to be normal parathyroid tissue. Twelve tissue samples did not confirm parathyroid tissue. The final histologic diagnosis in these 12 specimens were as follows: fat (n ⫽ 6), thyroid (n ⫽ 4), lymphatic (n ⫽ 1), and thymic (n ⫽ 1). Twenty-two of 119 patients at risk for developing postoperative hypocalcemia required calcium or calcitrol or both to maintain normocalcemia. During a median follow-up of 6 months, all patients reverted to normocalcemia without supplementation. A total of 264 thyroid lobes were examined. Eleven parathyroid tissue fragments (2.1%) were found attached to the resected thyroid lobes. Conclusions: Devascularized or inadvertently removed parathyroid glands can be accurately identified before autotransplantation. These glands should be immediately autotransplanted without the need for routine frozen section confirmation. Hypoparathyroidism can be avoided with this measure. Results suggest that implantation of lymph nodes or metastasis is unlikely.

REVIEWER SUMMARY Parathyroid autotransplantation was first described by Halsted in 1907.1 During the last 30 years, this operative strategy has increased in popularity. Today, it plays an CURRENT SURGERY • Volume 58/Number 1 • January/February 2001

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integral role in the operative management of certain parathyroid diseases and in the prevention of permanent hypoparathyroidism, a complication of thyroidectomy and parathyroidectomy.2-4 Advocates of this procedure4 point out its low incidence of permanent hypoparathyroidism and the ease in which portions of the grafted tissue can be excised in recurrent hypercalcemia (see Kinnaert et al abstract). There are several techniques and operative strategies employed in parathyroid autotransplantation. One common method is to slice the gland into 15 to 20 1 ⫻ 1 ⫻ 3-mm discs; alternatively, the gland can be minced prior to implantation.5,6 Intramuscular and subcutaneous placement have both been advocated (see Kinnaert et al abstract).6,7 The optimal location for transplantation is controversial. Forearm transplantation is convenient for graft excision and allows for accurate venous sampling in recurrent hyperparathyroidism.8 Sternocleidomastoid or pectoralis major muscle transplantation is simple and easily accessible.5 Several other anatomic locations have been reported and appear feasible. Cryopreservation of a portion of the parathyroid tissue adds a margin of safety in the event of graft failure regardless of the technique employed.9 Autograft function is typically undetectable for 2 to 3 weeks postoperatively. Vitamin D and calcium are often required in the immediate and short-term postoperative period until calcium levels stabilize.9 When subtotal parathyroidectomy is employed, this effect is often avoided. Maintenance of normal serum calcium levels, after calcium and vitamin D have been discontinued, is adequate clinical confirmation of graft function. In forearm transplants, function can be confirmed by a parathyroid hormone (PTH) gradient comparing venous outflow blood of the grafted and nongrafted limbs. A gradient of 1.5 or greater confirms graft function.10,11 The causes of primary hyperparathyroidism and its relative incidence are due to single adenoma (88%), multiple adenomas (3%), multiglandular hyperplasia (8%), and carcinoma (⬍1%). Surgical therapy remains the only effective treatment for each of these conditions. Most endocrine surgeons agree that single or multiple adenomas are best treated with excision of the abnormal glands only, leaving normal glands in situ. Parathyroid hyperplasia can occur sporadically or as a familial disease in multiple endocrine neoplasia types I and IIA.12 There are 2 treatment options for sporadic multiglandular hyperplasia: subtotal (3.5 gland) parathyroidectomy and total parathyroidectomy with autotransplantation. Familial disease is best managed with total parathyroidectomy and forearm autotransplantation.3,12 Parathyroid carcinoma requires an en bloc resection of all involved tissues including the ipsilateral thyroid lobe and isthmus.13 Contralateral parathyroid glands can be left in situ. Thirty percent of patients have palpable adenopathy and require a modified neck dissection. In those patients, total parathyroidectomy with autotransplantation may serve to prevent permanent hypoparathyroidism. Secondary hyperparathyroidism develops as a compensatory mechanism to correct chronically low plasma concentrations of ionized calcium. There is typically diffuse glandular hyperplasia and increased PTH secretion in response to renal disease, calcium malabsorption, and reduced phosphate excretion. Most patients (90% to 95%) can be managed medically.14 Subtotal parathyroidectomy or total parathyroidectomy with autotransplantation are both options for patients who fail medical management.15 The optimal surgical therapy is controversial. Tertiary hyperparathyroidism develops when these patients remain hyperparathyroid following successful renal transplantation. Tertiary and secondary disease can be approached similarly. Parathyroid autotransplantation has become an essential tool in the prevention of permanent hypoparathyroidism complicating cervical dissections and reoperative parathyroid surgery. The parathyroids are especially at risk of being inadvertently removed or devascularized during dissections for malignancies. Iatrogenic injury to the parathyroid glands during extensive thyroid surgery is the most common cause of permanent hypoparathyroidism. Most surgeons favor leaving normal glands in situ 18

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when feasible. When there is uncertainty regarding the blood supply, autotransplantation to the sternocleidomastoid muscle has been advocated.

D. KIRKLAND RAWL, MD JOSEPH B. COFER, MD Department of Surgery Chattanooga Unit of the College of Medicine University of Tennessee Chattanooga, Tennessee PII S0149-7944(00)00285-3

REFERENCES 1. Walker RP, Paloyan E, Kelley TF, Gopalsami C, Jarosz H. Parathyroid auto-

transplantation in patients undergoing a total thyroidectomy: a review of 261 patients. Otolaryngol Head Neck Surg 1994;111:258-264. 2. Wingert DJ, Friesen SR, Iliopoulos JI, et al. Post-thyroidectomy hypocalcemia:

incidence and risk factors. Am Surg 1986;152:606-610. 3. Olson JA, DeBenedetti MK, Baumann DS, Wells SA. Parathyroid autotrans-

plantation during thyroidectomy: results of long-term follow-up. Ann Surg 1996; 223:472-480. 4. Lo CY, Lam KY. Postoperative hypocalcemia in patients who did or did not

undergo parathyroid autotransplantation during thyroidectomy: a comparative study. Surgery 1998;124:1081-1086. 5. Funahashi H, Satoh Y, Imai T, et al. Our technique of parathyroid autotrans-

plantation in operation for papillary thyroid carcinoma. Surgery 1993;114:92-96. 6. Chou FF, Chan HM, Huang TJ, Lee CH, Hsu KT. Autotransplantation of

parathyroid glands into subcutaneous forearm tissue for renal hyperparathyroidism. Surgery 1998;124:1-5. 7. Kinnaert P, Salmon I, Decoster-Gervy, et al. Total parathyroidectomy and prest-

ernal subcutaneous implantation of parathyroid tissue for renal hyperparathyroidism. Surg Gynecol Obstet 1993;176:135-138. 8. Walgenbach S, Hommel G, Junginger T. Prospective evaluation of parathyroid

graft function after total parathyroidectomy and heterotopic autotransplantation in renal hyperparathyroidism by bilateral determination of intact parathormone in cubital venous blood. World J Surg 1998;22:93-98. 9. Feldman AL, Sharaf RN, Skarulis MC, et al. Results of heterotopic parathyroid

autotransplantation: a 13-year experience. Surgery 1999;126:1042-1048. 10. Sierra M, Herrera MF, Herrero B, et al. Prospective biochemical and scinti-

graphic evaluation of autografted normal parathyroid glands in patients undergoing thyroid operations. Surgery 1998;124:1005-1010. 11. Hidai H, Chiba T, Takagi Y, et al. Percutaneous autotransplantation of parathy-

roid tissue into the forearm muscles. Surg Today 1998;28:114-116. 12. Kaplan EL, Yashiro T, Salti G. Primary hyperparathyroidism in the 1990s: choice

of surgical procedures for this disease. Ann Surg 1992;215:300-317. 13. Rosen IB, Young JE, Archibald SD, Walfish PG, Vale J. Parathyroid cancer:

clinical variations and relationship to autotransplantation. Can J Surg 1994;37: 465-469. 14. Neonakis E, Wheeler MH, Krihman H, et al. Results of surgical treatment of

renal hyperparathyroidism. Arch Surg 1995;130:643-648. CURRENT SURGERY • Volume 58/Number 1 • January/February 2001

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15. Punch JD, Thompson NW, Merion RM. Subtotal parathyroidectomy in dialy-

sis-dependent and post-renal transplant patients: a 25 year single-center experience. Arch Surg 1995;130:538-542.

Laparoscopy Laparoscopic Inguinal Hernia Repair Guest Reviewer: James M. Nottingham, MD LAPAROSCOPIC MESH VERSUS OPEN PREPERITONEAL MESH VERSUS CONVENTIONAL TECHNIQUE FOR INGUINAL HERNIA REPAIR. Johansson B, Hallerback B, Glise H, et al. Ann Surg 1999;230:225-231. Objective: To evaluate the influence of the laparoscopic technique in hernia repair

regarding time to full recovery and return to work, complications, recurrence rate, and economic aspects. Design: A randomized, prospective multicenter study of 613 male patients for elec-

tive inguinal hernia repairs performed by many different surgeons. Setting: Ten hospitals in Sweden. Results: The men were randomly assigned to 1 of the 3 arms of the study (laparo-

scopic mesh, open preperitoneal mesh, or the conventional technique) with the goal of 200 patients per arm. Each group was similar in regard to age, weight, height, rate of direct inguinal hernia, and operative time. Of the 613 total patients enrolled in the study, 590 (96.2%) were participating at the 1-year follow-up. Postoperative parameters, including time to recovery, pain, physical restrictions, complications, and costs, were measured. The time to full recovery was less in the transabdominal preperitoneal (TAPP) group (p ⬍ 0.001) as was the sick leave time (p ⫽ 0.05) for the first 7 days. At 60 days, the groups showed no significant difference in the return to work. Pain at rest did not differ between the groups, although a trend existed for the open mesh group to have more pain at the 60-day follow-up. In regard to the restriction of physical activity, the TAPP group fared the best, with 40.9% reporting no restriction, whereas the open groups with a mesh showed a 28.5% report of no restriction at the 6-day visit and those without a mesh showed a 19.4% report. At 60 days, the difference was not significant. The complications in the TAPP group were minor, but more than the other 2 groups. Most of these complications were self-limited and required no intervention; however, long-term pain at 1 year seemed to be more than after the open techniques. The cost analysis showed the TAPP to be almost 6000 times the conventional hernia repair and 200 times the open mesh repair. Conclusions: A distinct, early advantage existed for the laparoscopic hernia repair

over the other anterior repairs in regard to time to return to work and to full activity. The advantage ended at the 8-week follow-up. Disadvantages appeared, including longer operative times, increased costs, and the need of general anesthesia. The complication potential, especially long-term pain, is worrisome. Individual evaluation will become more suitable for future hernia repairs.

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REVIEWER COMMENTS

This is a well-designed study with an uncorrectable flaw: The study cannot be double-blinded, which can introduce inherent bias into the study. The overall structure and endpoints were nicely illustrated. The several concerns that I have are that the surgeons participating in the study may not be high enough on the learning curve, which Voitk and associates1 and Kurzer and associates2 suggest may approach 50 cases instead of the 10 that these surgeons had done. The TAPP approach has fallen out of favor and given rise to the totally extraperitoneal (TEP) approach, which is the laparoscopic gold standard. In studies by Ramshaw and associates,3 Felix and associates,4 Fielding and associates,5 Dellemagne and associates,6 and Kald and associates,7 the TEP procedure shows less complications and recurrences than the TAPP, and this may have altered some of the results in this study. The cost issue is one that is difficult to tackle. Most studies have shown a higher cost associated with the laparoscopic repairs, but not this much. The anesthesia cost is now challenged by authors like Pendurthi and associates8 and Ferzli and associates,9 who have performed the TEP under local anesthesia. The authors have done a nice job with the statistics and have shown significance where it exists for return to work, pain, and restriction of activity. The complications may not be accurate because only 1-year of follow-up has occurred. The authors state that they will report a longer follow-up in 3 years.

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