Thompson, Geoffrey B.

AbstractSelected patients with primary hyperparathyroidism (pHPT) who have a positive preoperative sestamibi scan can be managed safely and successfully with a focused cervical exploration without either adjuvant intraoperative parathyroid hormone (PTH) monitoring or use of a gamma probe. This article reports a retrospective analysis of a consecutive series of patients surgically treated at a tertiary referral center. From August 1998 to August 2002, 100 patients (68 women, 32 men; mean age 63 years [range: 29–89 years]) underwent a focused cervical approach without intraoperative PTH monitoring or use of the gamma probe after perioperative sestamibi injection. The study group comprised 9% of all patients (n = 1063) undergoing cervical exploration for pHPT during the study period. Ninety patients underwent an initial exploration, and 10 others underwent repeat cervical exploration following prior parathyroid (n = 7) or thyroid (n = 3) operation. Sestamibi scanning correlated with one enlarged parathyroid gland in all patients. Other enlarged glands were, however, not demonstrated in three patients (true positive = 97%; false negative = 3%). The single enlarged glands excised in all patients had a mean weight of 795 mg (range: 90–3640) and were histologically compatible with an adenoma. Postoperatively, 97% of patients were eucalcemic. Three patients remained hypercalcemic (3%). Of the three patients with persistent hypercalcemia, one underwent successful re‐exploration with excision of a 500 mg second adenoma, whereas the other two patients (with confirmed familial HPT) remained hypercalcemic. Mean hospitalization was 0.5 days (range: 0–3 days). There was no operative mortality. No patients had permanent hypocalcemia. Postoperative morbidity occurred in three patients: two self‐limiting cervical hematomas and one permanent vocal cord paralysis. Selected patients with pHPT due to single‐gland disease and an unequivocally positive preoperative sestamibi scan can safely and successfully be managed with a focused unilateral cervical exploration without either intraoperative PTH monitoring or use of the gamma probe. Further experience with this surgical approach seems warranted to determine the overall cure rate, operative morbidity, and the sensitivity and specificity of preoperative localization studies.

AbstractGushing syndrome (CS) caused by ectopic adrenocorticotropic hormone (ACTH) production (EA) poses major challenges diagnostically by mimicking the pituitary‐dependent form of CS and therapeutically by producing severe, life‐threatening hypercortisolemia. This retrospective follow‐up study describes the clinical characteristics and course of EA in a large referral center. Computer‐based cross‐index codes for EA, CS, and bilateral adrenalectomy were used to identify patients treated at the Mayo Clinic between 1956 and 1998. EA was confirmed in 106 patients. Gender distribution showed a slight female predominance (61:45). Bronchial carcinoid was the most frequent cause of EA (25%), followed by islet cell cancer (16%), small‐cell lung carcinoma (11%), medullary thyroid cancer (8%), disseminated neuroendocrine tumor of unknown primary source (7%), thymic carcinoid (5%), pheochromocytoma (3%), disseminated gastrointestinal carcinoid (1%), and other tumors (8%). No tumor was found in 16% of patients. Altogether, 28 patients were managed medically, and the others underwent curative tumor resection (13 patients) or bilateral adrenalectomy (65 patients). Surgically treated patients had longer survival, but this was most likely affected by treatment bias. The diagnoses of CS and ACTH‐secreting neoplasm were usually concurrent, although, there were remarkable cases in which the two conditions were diagnosed several years apart. Curative resection of the tumor producing EA was possible in a small proportion of patients (12%). When curative resection is not possible, patients who are reasonable surgical candidates are likely to benefit from adrenalectomy. Additional experience with bilateral laparoscopic adrenalectomy should increase the number of patients who benefit from adrenal‐directed surgery.

Abstract Background Papillary thyroid cancer (PTC) has a generally favourable prognosis, but elderly patients with distant metastases or extracapsular invasion fair poorly. In small studies with short follow-up, young patients presenting with such extracapsular invasion and pulmonary metastases have faired well. This retrospective study was undertaken to clarify the long-term prognosis of such patients with advanced PTC. Methods Twenty-one children and young adults (median age 14 (range 6–20) years) presenting with PTC and pulmonary metastases were treated at a single institution between 1947 and 1998. Mean maximal tumour diameter was 4·65 cm. Initial surgical treatment consisted of total thyroidectomy (n = 16), subtotal thyroidectomy (n = 4) and isthmectomy (n = 1), coupled with a variety of lymph node dissections (n = 20). After operation, 19 patients were treated with ablative and incremental doses of iodine-131 until disease free. All patients were placed on suppressive thyroid hormone after operation. Mean length of follow-up was 21 years (range 3 months to 47 years). Follow-up was less than 3 years in four patients. All patients have undergone post-treatment radionucleotide and radiological evaluation. Results Nine of the 21 patients developed recurrent disease. The risk of recurrence at 5 years was 39 (95 per cent confidence interval 14–57) per cent. Eight had cervical lymph node recurrence and no patient developed recurrent pulmonary disease. All patients with identifiable recurrent disease underwent selective lymph node resection, which involved multiple resections in four. At follow-up, 18 patients remain completely free of disease, one patient has recurrent cervical node disease and two patients have died. The disease-free survival at 5 years was 95 (95 per cent confidence interval 86–100) per cent. Cause-specific death occurred in a single patient who died from extensive local disease at age 29 years after 12 years of multiple cervical lymph node recurrences. Conclusion A stepwise treatment approach including total thyroidectomy, high-dose iodine-131 treatment and early surgical reintervention for suspected local recurrent disease allows long-term survival and frequent ‘cure’ for young patients with PTC and concomitant pulmonary metastases.

Abstract Background The authors have reported a newly recognized hypoglyacemic disorder, non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), which is characterized by postprandial hyperinsulinaemic hypoglycaemia, negative 72-h fast, negative transabdominal and intraoperative ultrasonography, spiral computed tomography and coeliac axis angiography, positive selective arterial calcium stimulation test (SACST), absence of insulinoma but presence of islet hypertrophy and nesidioblastosis, and relief of symptoms from gradient-guided partial pancreatectomy. Experience with the next five patients with this disorder (6–10; 1998–1999) compared with the original five (1–5; 1996–1998) is reported. Results Wide age range, male predominance, postprandial occurrence of symptoms, negative radiological localization, nesidioblastosis/islet hypertrophy, but no insulinoma characterized all ten cases. Response to SACST indicated widespread islet hyperfunction in patients 1 and 5; limitation to distribution of the SPA and GDA in patients 3, 4, 6 and 8, to distribution of the SPA in patients 2, 7 and 9, and to distribution of the SMA in patient 10. Except for patient 5, pancreatic resection to the left of the SMV was performed when only the SPA was positive on the SACST. Patients 5 and 8 have had recurrence of symptoms; they resolved within 3 months for patient 5. Conclusion NIPHS can usually be treated successfully with gradient-guided partial pancreatectomy.

The trend toward limited exploration for primary hyperparathyroidism (1° HPT) has stemmed from advances in sestamibi scanning, gamma probe technology, and intraoperative parathyroid hormone monitoring (iPTH). Prior to widespread application, directed parathyroidectomy must be shown to meet the high standards of conventional cervical exploration. In this prospective, nonrandomized trial, results of parathyroidectomy utilizing the gamma probe, iPTH, or neither technique were evaluated. Altogether, 150 patients underwent parathyroidectomy utilizing the gamma probe (n = 50), iPTH (n = 50), or neither technique (n = 50). Each group was evaluated for operating time, length of hospitalization, cure rate, morbidity, mortality, and cost. A telephone survey was conducted with 25 patients in each group (n = 75) to address patient satisfaction. The gamma probe localized the abnormal gland in 66% of patients and confirmed cure intraoperatively in 84%. In the iPTH group, a more than 50% decrease from baseline occurred in 98%. The mean operating times were 76, 84, and 90 minutes, respectively (p = 0.16); and the mean length of hospitalization was 1 day. The biochemical cure rates were 98%, 100%, and 96%, respectively (p = 0.17). Total costs were $4476, $3918, and $3905, respectively. A total of 96% of patients in all three groups were "very satisfied" with their surgical procedure. Directed parathyroidectomy utilizing the gamma probe or iPTH assay does not significantly alter the operating time, length of hospitalization, cure rate, morbidity, mortality, or patient satisfaction when compared to conventional exploration in our practice. The probe is more expensive and was not a consistently reliable tool for localizing parathyroid pathology. PTH monitoring reliably predicts cure intraoperatively.

It is uncertain whether more extensive primary surgery and increasing use of radioiodine remnant ablation (RRA) for papillary thyroid carcinoma (PTC) have resulted in improved rates of cause‐specific mortality (CSM) and tumor recurrence (TR). Details of the initial presentation, therapy, and outcome of 2444 PTC patients consecutively treated during 1940–1999 were recorded in a computerized database. Patients were followed for more than 43,000 patient‐years. The 25‐year rates for CSM and TR were 5% and 14%, respectively. Temporal trends were analyzed for six decades. During the six decades, the proportion with initial MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) scores <6 were 77%, 82%, 84%, 86%, 85%, and 82%, respectively (p = 0.06). Lobectomy accounted for 70% of initial procedures during 1940–1949 and 22% during 1950–1959; during 1960–1999 bilateral lobar resection (BLR) accounted for 91% of surgeries (p <0.001). RRA after BLR was performed during 1950–1969 in 3% but increased to 18%, 57%, and 46% in successive decades (p <0.001). The 40‐year rates for CSM and TR during 1940–1949 were significantly higher (p = 0.002) than during 1950–1999. During the last 50 years the 10‐year CSM and TR rates for the 2286 cases did not significantly change with successive decades. Moreover, the 10‐year rates for CSM and TR were not significantly improved during the last five decades of the study, either for the 1917 MACIS <6 patients or the 369 MACIS ? 6 patients. Increasing use of RRA has not apparently improved the already excellent outcome, achieved before 1970, in low risk (MACIS <6) PTC patients managed by near‐total thyroidectomy and conservative nodal excision.

AbstractThis prospective randomized study examined the acute‐phase response and wound healing, comparing laparoscopic (LA) and open posterior (PA) adrenalectomy in a cushingoid porcine model. Repository corticotropin gel was given to 40 pigs for 21 days. Biochemical and tissue parameters of Cushing syndrome were confirmed. The pigs were randomized to undergo LA or PA. In addition to operating time and morbidity, the acute‐phase response was compared by measuring the postoperative white blood cell count, fasting glucose, C‐reactive protein, and nitrogen balance. Wound healing was assessed by (1) scored (1–4) gross appearance at 48 hours and 1 and 2 weeks; (2) histologic examination; and (3) tensile strength. There was no difference in operating time (mean ± SD) (36 ± 9 minutes open vs. 37 ± 7 minutes laparoscopic), perioperative mortality, degree of leukocytosis, fasting glucose, or C‐reactive protein (p > 0.05). Nitrogen balance, wound scores, and tensile strength at 24 hours and 1 week were more favorable in the LA group than in the PA group (p < 0.05). In the cushingoid porcine model, laparoscopic adrenalectomy was less catabolic and was associated with fewer wound complications than the open posterior adrenalectomy. These findings provide support for continued pursuit of laparoscopic methods for adrenalectomy in the clinical setting.

AbstractWe currently recommend excision of adrenal incidentalomas ≥ 4 cm in size and all hormonally active tumors. The optimal management and follow‐up of smaller nonfunctioning tumors are controversial. The aim of this study was to determine the clinical outcome of a well defined population of patients with incidentalomas followed without operative intervention. The study group comprised 231 patients, identified from the records of abdominal or thoracic computed tomographic (CT) scans performed between 1985 and 1989. The primary outcome variable analyzed was survival. Follow‐up was obtained by office records, telephone contact, or letter. There were 101 male and 130 female patients with a mean age at diagnosis of 64 years (range 5–86 years). Most adrenal tumors were unilateral (right 113; left 98); 20 were bilateral. Mean tumor size was 2 cm (range 1–6 cm). In nine (4%) patients the tumor was ≥ 4 cm. Follow‐up [mean 7 years; range 1 month (patient died) to 11.7 years] was complete in 224 (97%) patients. Ninety‐one (39%) patients had one or more additional CT scans performed during the follow‐up period, with only four patients demonstrating a > 1 cm increase in the size of the adrenal mass. Surgical excision of these four lesions identified benign pathology. Eighty‐one (35%) patients died of conditions unrelated to adrenal pathology. No patient developed subsequent adrenal hyperfunction or adrenal malignancy. Within the context of our guidelines, conservative management of adrenal incidentalomas considered benign or nonfunctioning at diagnosis is appropriate. Additional information provided by repeat CT scanning appears to confer limited benefit. This study does not support laparoscopic removal of small, nonfunctional adrenal tumors, as has been suggested.

AbstractIslet cell carcinoma (ICC) of the pancreas is a rare, indolent malignancy associated with higher resectability rate and better survival than ductal carcinoma. This retrospective study presents results of surgical treatment from a single institution. From 1985 through 1993 a total of 64 patients (36 men, 28 women) were surgically treated for ICC. Ages ranged from 22 to 80 years (median 55 years) with a median postoperative follow‐up of 39 months (range 10–97 months). Of the 64 patients, 30 (47%) had functioning and 34 (53%) nonfunctioning tumors. Gastrinoma (n= 11) followed by glucagonoma (n= 6) and insulinoma (n= 4) were the most common functioning tumors. In the patients undergoing a laboratory study, 67% of the nonfunctioning tumors had elevated peptide hormone levels. Potentially curative resections were performed in 17 patients (26%), palliative procedures in 35 (55%), and exploratory laparotomy alone in 12 (19%). One patient (2%) died within 30 days after operation. Symptomatic improvement was achieved in 96% of patients with a mean duration of 22 months. Three‐ and five‐year survivals were 66% and 49%, respectively. In patients with curative resection, the disease‐free survival at 3 years was 53% (95% CI: 32–86%). The presence of diffuse hepatic metastases was a predictor of poor survival at 3 years (74% versus 58%;p= 0.05); there was no statistically significant difference in survival between functioning and nonfunctioning groups (p> 0.1). Although curative resection for ICC is rare, meaningful palliation can be achieved in most patients with rare mortality and acceptable morbidity.

AbstractMultiple endocrine neoplasia type I (MEN‐I) is an autosomal dominant disorder characterized by endocrinopathies involving the anterior pituitary gland, parathyroid glands, and pancreas. The long‐term prognosis for patients affected with this disorder is uncertain. To better characterize this prognosis, we performed a retrospective review of all patients with MEN‐I treated at a single institution during the period 1951–1997. A group of 233 patients served as the study population. Their records were analyzed for confirmation of diagnosis, treatments received, long‐term survival, and cause of death. Altogether, 108 eight male patients (46%) and 125 female patients (54%) were identified. At the conclusion of the study, 164 (70%) were alive and 69 (30%) were deceased, with a median follow‐up for patients alive at last contact of 13.4 years (range < 1 month to 54.3 years). The cause of death was reliably obtained in 60 patients. Of these patients, 17 (28%) died of causes related to MEN‐I, most commonly metastatic islet cell tumors (10 patients). The remaining patients died of causes unrelated to MEN‐I, most commonly coronary artery disease and nonendocrine malignancies (14% each). The overall 20‐year survival of MEN‐I patients was 64% (95% CI was 56–72%), and that of an age‐ and gender‐matched upper Midwest population was 81% (p < 0.001). Patients with MEN‐I appear to be at increased risk of premature death. Earlier diagnosis and treatment of potentially malignant pancreatic islet cell neoplasms may result in a decrease of this premature mortality.