Grant, Clive S.

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.

AbstractFunctioning extraadrenal paragangliomas represent more than 10% of all pheochromocytomas, occur at diverse anatomic locations, and are said to have a higher malignancy rate than intraadrenal pheochromocytomas. Sixty‐six patients had surgery for catecholamine‐producing paragangliomas between 1952 and 1992. Median follow‐up was 8.8 years. Median age was 40 years (11–67 years); the male/female ratio was 29:37. Familial disease occurred in 9 patients (13.6%), and 10 patients (15.2%) also developed adrenal pheochromocytoma. Solitary paragangliomas occurred in 52 patients: 46 abdominal, 4 thoracic, and 2 head and neck. Fifty‐three tumors developed in 14 patients with multiple paragangliomas: 38 abdominal and 15 thoracic. Of 28 patients with solitary tumors undergoing localization studies over the past 10 years accurate localization was achieved in 27. There was one operative death; 15 patients had persistent disease; and 50 were cured postoperatively. Of those cured, nine developed recurrence, disease‐free survival being 86%, 80%, and 80% at 5, 10, and 20 years. Metastatic disease was found in 14 patients (21%), 7 of whom have died. An additional 10 patients (15%) had locally invasive disease, of whom 4 have died. Cause‐specific survivals at 5, 10, and 20 years were 90%, 83%, and 72%. Risk factors for death from pheochromocytoma were tumor size > 5 cm (p= 0.0002), metastatic disease (p= 0.001), and tumor invasion (p= 0.0023). Cause‐specific survival for patients with tumors > 5 cm was 59% at 15 years compared to 100% among patients with tumors ≤ 5 cm (p= 0.0003). Functional paragangliomas are frequently malignant and are associated with a high incidence of persistent or recurrent disease. Tumor size > 5 cm and the occurrence of invasive or metastatic disease are strong predictors of outcome. Most tumors are abdominal, and imaging is highly successful for localization.

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.

AbstractEighty‐two children and adolescents (18 males, 64 females; median age 14 years) surgically treated for Graves’ disease at a single institution between 1979 and 1993 were retrospectively reviewed. Most of the patients (74%) coming to thyroidectomy had been treated medically for a period ranging from 2 to 80 (median 15) months. Bilateral subtotal thyroid resection was the most frequently performed procedure (86%). Postoperatively, no permanent recurrent laryngeal nerve palsy or permanent hypocalcemia occurred. Operative mortality was zero. With a median follow‐up of 8.3 years, recurrent hyperthyroidism occurred in five patients (6%), one of whom required reoperation. Most children and adolescents with Graves’ disease can be rendered euthyroid by nonsurgical treatment options. However, prolonged and ineffective medical treatment should be avoided in these patients who are in the formative years of their lives. Surgical treatment, when indicated and employed, offers young patients with Graves’ disease a safe, rapid, definitive, cost‐effective treatment with a high success rate.

AbstractSurgical treatment for adrenal disease may be withheld from elderly patients because of concern about prohibitive operative morbidity and mortality. To obtain objective data in our practice, we analyzed the results of adrenalectomy for patients aged 65 years and older. From 1984 to 1993 there were 85 patients (41 men, 44 women) with ages ranging from 65 to 84 years (median 69 years) who underwent adrenalectomy for Cushing syndrome (n= 19), pheochromocytoma (n= 16), adrenocortical carcinoma (n= 7), benign adenoma (n= 26), or primary hyperaldosteronism (n= 17) at our institution. Median follow‐up was 26 months (range 1 month to 9.1 years). A retrospective review with respect to preoperative risks and postoperative morbidity and mortality was performed utilizing the American Society of Anesthesiologists (ASA) physical status classification and the modified Goldman multifactorial cardiac risk scheme. Survival was estimated by the Kaplan‐Meier methods. Operative mortality was 7% (six patients). No patients with pheochromocytoma or primary hyperaldosteronism died during the postoperative period. Patients undergoing adrenalectomy for adrenocortical carcinoma had a significantly higher operative mortality (43%) (p= 0.006). Postoperative complications developed in 19 patients (22%), and there was a reoperation rate of 6% (5 patients). Nineteen percent of patients required postoperative intensive care admission and had a median stay of 2 days (range, 1–38 days). Median hospital stay was 7 days (range 3–47 days). Seventy‐three patients (86%) remained alive at study completion. Two‐ and five‐year survivals were 86% and 84%, respectively. Goldman class II or greater was an excellent predictor of increased morbidity (p= 0.032) and mortality (p= 0.036). With the exception of adrenocortical carcinoma, adrenal surgery for elderly patients can be performed with acceptable morbidity and mortality. The Goldman multifactorial cardiac risk scheme reliably predicts postoperative outcome in this elderly group of patients.

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.