Inappropriate medicine prescribing in older South Africans: A cross-sectional analysis of medicine claims data.

BACKGROUND: Prescribing for older patients is a well-recognised problem, and inappropriate items are prescribed frequently. Several tools and criteria are available to promote rational prescribing in older patients. OBJECTIVE: To determine the prevalence of potentially inappropriate prescriptions (PIPs) in older South African patients. METHODS: A retrospective drug utilisation review was conducted using medicine claims data over a 1-year period. Patients aged ≥65 years with at least one paid claim for any medicine item during this period were included. The prevalence of PIPs was identified by applying the 2012-Beers criteria list. RESULTS: A total of 103 420 patients, mean age 74.0 years (standard deviation 6.7), 57.1% female, were included in the analysis. The number of PIPs identified was 562 852 in 71 206 patients (68.9%). The most common medicines inappropriately prescribed were oestrogen (oral and patch formulations only) (12.4%), meloxicam (7.3%), amitriptyline and combinations thereof (6.5%), diclofenac (6.4%), ibuprofen (6.1%), alprazolam (5.3%), meprobamate and combinations thereof (5.0%), sliding-scale insulin (3.3%), amiodarone (3.1%) and doxazosin (2.6%). Medicines were inappropriately prescribed to women statistically significantly more often than to men (1.9:1; p<0.001), although this difference was not of practical significance (Cramér's V=0.06). CONCLUSIONS: Medicine use in older patients must be appropriate and evaluated regularly. According to explicit criteria, PIPs were found to be common in older patients registered on the database. Monitoring of PIPs may increase the quality of prescribing, but explicit criteria cannot substitute for clinical judgement based on the individual patient.

Cushing's syndrome due to medullary thyroid carcinoma: diagnosis by proopiomelanocortin messenger ribonucleic acid in situ hybridization.

Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). Serum calcitonin was 1597 pg/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 micro g/d), epinephrine (66 micro g/d), and calcium (558 mg/d). Baseline serum cortisol was 23.9 micro g/dl and decreased to 12.9 and 4.5 micro g/dl after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 170 pg/ml and decreased to 75 and 24 pg/ml after dexamethasone. Bone density t-score was -4.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. Magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. Serum CRH was less than 6.6 pg/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 micro g/d), epinephrine (0 micro g/d), and calcium (281 mg/d) but not plasma ACTH (125 pg/ml). Neck dissection reduced calcitonin by 96% (5300 to 120 pg/ml) and ACTH by 91% (125 to 11 pg/ml). Carcinoembryonic antigen was reduced from 32.0 to 2.3 ng/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing's syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.

Reexploration for symptomatic hematomas after cervical exploration.

BACKGROUND: Hematomas requiring reoperation affect 1% of patients undergoing cervical exploration. This complication has implications for the trend toward outpatient procedures. METHODS: Retrospective review of 13,817 patients undergoing thyroidectomy and parathyroidectomy at this institution (1976 to 2000) identified 42 patients with hematomas requiring reoperation. Case controls (n = 42) were matched for age, gender, and type and year of operation. Perioperative risk factors and outcome were compared. RESULTS: Study and control groups were composed of 18 men and 24 women (mean age, 62 years) undergoing thyroidectomy (n = 21) or parathyroidectomy (n = 21). Comparison of perioperative risk factors yielded no significant difference between groups. Symptoms included respiratory distress in 21 patients, pain/pressure in 11, dysphagia in 8, and drainage in 6. Mean time to symptom onset was 17 hours (range, 10 minutes to 5 days). Eighteen hematomas presented within 6 hours postoperatively, 16 between 7 and 24 hours, and eight beyond 24 hours. The bleeding source was arterial in 11 patients, venous in 8, thyroid/soft tissue in 13, and indeterminate in 10. Mean hospital stay was longer in the study group (7.2 vs 3.6 days, P = .004). The number of patients with complications was higher in the study group (17 vs 7, P = .03). No single complication reached significance: hypocalcemia (8 vs 3, P = .12), wound infection (3 vs 0, P = .87), and others (10 vs 5, P = .21). CONCLUSIONS: (1) No factor foreshadowed this complication. (2) The definition of a high-risk population remains obscure. (3) Sixty percent presented beyond 6 hours postoperatively. (4) Reexploration increased morbidity and lengthened hospital stay.

Anaplastic thyroid carcinoma: a 50-year experience at a single institution.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is among the most aggressive of human malignancies. However, there have been few large studies of histologically well-defined ATC. We report the results of a 50-year experience of this lethal malignancy. METHODS: We reviewed all cases of ATC managed in this institution between 1949 and 1999. One pathologist (J.R.G.) reviewed all pathologic material. Clinical details were obtained from medical records, and current status of all patients was determined. RESULTS: There were 134 cases, with a female-to-male ratio of 1.5:1 and a mean age of 67 years. Benign thyroid disease was present in 27 cases (20%) and well-differentiated thyroid carcinoma in 31 (23%). Sixty-two patients (46%) had distant metastases at diagnosis, and 98% of the tumors were locally invasive. Primary treatment was surgical for 96 patients (72%). Complete resection was achieved in 29 cases (30%), with "minimal residual disease" in 25. Neither extent of operation nor completeness of resection affected survival (P > .4). Postoperative radiotherapy gave slightly longer median survival (5 vs 3 months), which was not significant (P < .08). Multimodal therapy, including operation, chemotherapy, and radiotherapy, did not improve survival. CONCLUSIONS: The outlook for patients with ATC remains grim. Novel treatments for ATC are desperately needed.

Benign paragangliomas: clinical presentation and treatment outcomes in 236 patients.

Paragangliomas are rare tumors that arise from extraadrenal chromaffin cells. We examined the clinical characteristics, location, treatment, and outcome of 236 patients (141 females, 60%) with 297 benign paragangliomas evaluated at the Mayo Clinic during 1978-1998. The mean age (+/-SD) at diagnosis was 47 +/- 16 yr. Of the 297 paragangliomas, 205 were in the head and neck region, and 92 were below the neck. Paragangliomas were discovered and diagnosed incidentally on imaging studies in 9% of patients. Biochemical screening was performed in 128 patients; 40 patients (17% of the total and 31% of those screened) had hyperfunctional tumors. Of the 40 patients with tumoral catecholamine excess, 38 had documented hypertension. In patients identified with catecholamine-secreting paragangliomas, the sensitivities achieved by measurements in the 24-h urine collection were 74% for total metanephrines, 84% for norepinephrine, 18% for dopamine, and 14% for epinephrine. Multiple imaging modalities were used for tumor localization. The false negative rates were 0% for magnetic resonance imaging, 5.8% for computed tomography, 3.4% for angiography, 10.7% for ultrasonography, and 39% for radioactive iodine-labeled metaiodobenzylguanidine scintigraphy. Of 192 patients (81.4%) with follow-up data (mean, 43.9 months; range, 0.5-240), operative cure was achieved in 133 (69%). Of the 59 patients without cure, 23 had persistent disease, 5 had recurrent disease, 16 had multiple persistent synchronous tumors, and 15 subsequently developed metachronous tumors. In conclusion, most paragangliomas are nonhypersecretory and located in the head and neck region. Magnetic resonance imaging was associated with the lowest false negative rate, and metaiodobenzylguanidine was the least sensitive imaging study. A significant proportion of patients (31%) has persistent or recurrent disease, and long-term follow-up is important.

Cushing syndrome due to ectopic adrenocorticotropic hormone secretion.

Cushing 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.

Primary aldosteronism: factors associated with normalization of blood pressure after surgery.

BACKGROUND: Hypertension often persists after adrenalectomy for primary aldosteronism. OBJECTIVE: To determine factors associated with resolution of hypertension after adrenalectomy for primary aldosteronism. DESIGN: Retrospective cohort study. SETTING: Tertiary care referral center in Rochester, Minnesota. PATIENTS: All patients who underwent adrenalectomy for primary aldosteronism between 1 January 1993 and 31 December 1999. MEASUREMENTS: Preoperative plasma renin activity, plasma and urinary aldosterone concentrations, and adrenal imaging. Follow-up blood pressure, measured at a clinic visit or at home, was reviewed. RESULTS: 97 adrenalectomies were performed, and follow-up was available in 93 patients. Hypertension was resolved at follow-up (blood pressure < 140/90 mm Hg) without use of antihypertensive agents in 31 of 93 patients (33%). According to a stepwise multivariable logistic regression analysis adjusted for duration of follow-up, resolution of hypertension was independently associated with family history of hypertension in no more than 1 first-degree relative (odds ratio [OR], 10.9; P < 0.001) and preoperative use of two or fewer antihypertensive agents (OR, 4.7; P = 0.005). Additional factors associated with resolution of hypertension based on univariate analysis included younger age, shorter duration of hypertension, higher preoperative ratio of plasma aldosterone concentration to plasma renin activity, and higher urine aldosterone level (P < 0.05). CONCLUSIONS: Resolution of hypertension after adrenalectomy for primary aldosteronism is independently associated with a lack of family history of hypertension and preoperative use of two or fewer antihypertensive agents.

Adrenocortical carcinoma: surgical progress or status quo?

HYPOTHESIS: Outcome of patients with adrenocortical carcinoma (ACC) has improved with the advent of more widely available and higher quality imaging. Operative management strategies and use of adjuvant therapy have not changed. DESIGN: Retrospective review of patient histories, imaging studies, operative data, adjuvant therapy, and outcomes at a single institution. Follow-up was complete for a mean of 53 months. Data was compared with prior institutional experience. SETTING: Tertiary care referral center. PATIENTS: All patients undergoing operative management for ACC during the period from 1980 to 1996. MAIN OUTCOME MEASURES: Determinants of recurrence, survival, and the effect of adjuvant therapy on overall outcome. RESULTS: Fifty-eight patients (30 men, 28 women) with a mean age of 53 years underwent primary operative management for ACC. Functional tumors were identified in 27 patients (47%). Mean tumor size was 12.5 cm. Stage according to the TNM staging system (AJCC Cancer Staging Manual) at presentation was I (n = 0), II (n = 30), III (n = 7), and IV (n = 21). Surgical management included curative resection in 41 (71%), noncurative resection in 14 (24%), and open biopsy in 3 (5%). Perioperative mortality was 5%. Recurrence occurred in 30 patients (73%) with a median time to recurrence of 17 months. Five-year survival by the Kaplan-Meier method was 37%. Prognostic factors (P<.05) included functional status, stage, and chemotherapy in stage III/IV patients. When compared with our prior institutional experience (1960-1980), current patients were more likely to present with stages I to II (52% vs. 34%), have curative resections (71% vs. 50%), and have improved 5-year survival (37% vs. 16%). CONCLUSIONS: (1) Surgical resection remains the principal treatment for stage I to III disease. (2) Adjuvant therapy may improve survival in patients with stage III or IV disease. (3) Current patients were more likely to present at an earlier stage, undergo curative resections, and have improved 5-year survival than institutional historical comparisons.

Surgical management of duodenal leiomyomas.

Duodenal leiomyomas are rare neoplasms and when present are usually asymptomatic. There are, however, isolated case reports of such leiomyomas giving rise to complications including gastrointestinal hemorrhage and obstruction. The purpose of this study was to review the surgical experience with duodenal leiomyomas at a large tertiary referral center. A retrospective review was performed of all patients with histologically proven duodenal leiomyomas encountered from 1975 to 1995. Twelve patients with surgically treated duodenal leiomyomas were identified. There were eight men and four women with a mean age of 57 years (range 20-73 years) at diagnosis. Anemia was the presenting sign in 10 patients (83%). The mean hemoglobin level at presentation was 10.8 +/- 2.67 g/dl. Other presenting signs included melena (n = 5) and epigastric tenderness (n = 4). No patient had obstructive symptoms. Upper endoscopy visualized the lesion in 9 of 10 patients, but endoscopic biopsy provided an accurate histologic diagnosis in only two of six patients biopsied. All resected specimens underwent frozen section and permanent histopathologic analysis. Local excision was performed in eight patients, as benignancy was anticipated at surgical exploration and frozen section findings. Two patients underwent segmental duodenal resection with primary end-to-end anastomosis, and two patients underwent a Whipple procedure. There was no perioperative mortality. Morbidity was minimal. There was no tumor recurrence during a median follow-up of 8.4 years. Gastrointestinal blood loss is the most common complication of duodenal leiomyomas requiring surgical intervention. Small symptomatic leiomyomas with benign features may be safely treated with local excision.

Laparoscopic adrenalectomy for adrenocorticotropin-dependent Cushing's syndrome.

Bilateral adrenalectomy is indicated for the treatment of ACTH-dependent Cushing's syndrome when the tumorous source of ACTH hypersecretion cannot be identified or removed. Potential advantages of laparoscopic over open adrenalectomy include shorter hospitalization, decreased requirement for postoperative analgesia, and decreased postoperative morbidity due to incisional complications. Bilateral laparoscopic adrenalectomy performed for the treatment of ACTH-dependent Cushing's syndrome was attempted in 19 patients at our institution between 1995 and 1998. Conversion to an open procedure was required in three patients. All patients who underwent bilateral laparoscopic adrenalectomy were subsequently followed to assess the outcome of this intervention. Twelve patients with pituitary-dependent Cushing's syndrome and four with ectopic ACTH syndrome underwent successful bilateral laparoscopic adrenalectomy. All patients experienced resolution of the signs and symptoms (e.g. proximal myopathy, hirsutism, and emotional lability) of Cushing's syndrome as well as weight loss, improved glucose tolerance, and improved control of blood pressure. No residual cortisol secretion was detected in the patients. Bilateral laparoscopic adrenalectomy is a safe and effective treatment for Cushing's syndrome when the ACTH-secreting neoplasm cannot be removed.

Risk of parathyromatosis after fine-needle aspiration.

Reoperative surgery for hyperparathyroidism (HPT) is fraught with hazard. When preoperative imaging studies are inconclusive or patient comorbidities are extensive fine needle-aspiration (FNA) is helpful to confirm the presence of suspected parathyroid tissue in the neck. Some surgeons refrain from using FNA because of the concern of tissue implantation (parathyromatosis). A retrospective review (1984-1996) of all patients diagnosed with HPT undergoing FNA of suspected parathyroid tissue was performed to document whether a correlation exists between FNA of suspected parathyroid tissue and subsequent development of parathyromatosis. Parathyromatosis was considered to have occurred when proven by histology or suspected on the basis of clinical studies. Of 81 patients with HPT undergoing ultrasound-guided FNA to assess abnormalities in the neck 41 patients with confirmed parathyroid tissue were identified. The indications for FNA in these 41 patients were: prior failed cervical exploration (n = 33), prior neck surgery and/or radiation (n = 2), inconclusive noninvasive imaging studies (n = 15), and severe comorbidities (n = 8). Mean follow-up was 5.8 years. No case of FNA-induced parathyromatosis was identified. FNA is useful to confirm the presence of parathyroid tissue in very select patients with hyperparathyroidism. FNA often eliminates the need for other imaging studies, may prevent a needless or likely fruitless re-exploration, and does not cause parathyromatosis.

Pathologic features and expression of insulin-like growth factor-2 in adrenocortical neoplasms.

We analyzed a series of adrenocortical neoplasms to compare the clinicopathologic features and the expression of insulin-like growth factor-2 (IGF-2) in adrenocortical adenomas and carcinomas. IGF-2 is a growth factor commonly expressed in many tumors including adrenal cortical and medullary neoplasms. Formalin-fixed paraffin-embedded tissues from 64 adrenocortical adenomas and 67 adrenocortical carcinomas were analyzed. The carcinomas were histologically graded from 1 to 4 based on mitotic activity and necrosis. Tumor weight, size, and follow-up information were obtained by chart review. Expression of IGF-2 was detected by immunohistochemistry with the avidin-biotin-peroxidase complex method and a monoclonal antibody against IGF-2. Adrenocortical carcinomas were larger (mean: 13.1 cm, 787 g) than adenomas (mean: 4.2 cm, 52 g) (p < 0.001). Inpatients with adrenocortical carcinomas, high tumor grade (3 or 4) (p = 0.01) was associated with decreased survival. Expression of IGF-2 was higher in adrenocortical carcinomas than in adenomas (p < 0.001). These results show that tumor size and weight along with expression of IGF-2 protein are useful features to assist in distinguishing between adrenocortical adenomas and carcinomas, and that high tumor grade is a predictor of survival in adrenocortical carcinomas. However, single immunohistochemical markers such as IGF-2 or single histopathologic features cannot by themselves separate adrenocortical adenomas from carcinomas, and a combination of clinical, gross, and microscopic features are needed to establish the diagnosis in difficult cases.

Nondiagnostic thyroid fine-needle aspiration cytology: management dilemmas.

Approximately 10% to 20% of thyroid biopsies by fine-needle aspiration (FNA) are nondiagnostic. The management of thyroid nodules in which FNA is nondiagnostic remains controversial because few studies have addressed this issue. We retrospectively reviewed the medical records of 153 patients with nondiagnostic FNAs of the thyroid performed in 1994. Sixty patients had reaspiration biopsies performed. Thirty-seven specimens (62%) were diagnostic and 23 (38%) remained nondiagnostic. Of the 27 patients who had a thyroid operation, 10 (37%) had a malignancy. Preoperative information about physical examination, ultrasound imaging, or nondiagnostic FNA did not predict outcome. Nondiagnostic FNAs of the thyroid may be associated with a high probability of thyroid malignancy. Nondiagnostic FNAs should not be considered benign. Reaspiration followed by selective surgical treatment is recommended.

Papillary thyroid cancer with pulmonary metastases in children: long-term prognosis.

BACKGROUND: Papillary thyroid cancer (PTC) in young patients may rarely be encountered with pulmonary metastases. Previous studies have suggested that, in the pediatric population, this may not portend a lethal outcome. Our present study, children with pulmonary metastases, was designed to clarify this issue. METHODS: Fourteen children and young adolescents (mean age, 13.5 years; range, 9.8-17 years) with PTC and pulmonary metastases were treated at our institution between 1937 and 1998. Surgical treatment consisted of total thyroidectomy (n = 10 patients), subtotal thyroidectomy (n = 3 patients), and a biopsy only procedure (n = 1 patient). All patients who underwent thyroidectomy also underwent a variety of cervical lymph node dissections, and all patients proved to have regional nodal disease. After the operation, 12 patients were treated with ablative doses of (131)I, 1 patient was treated with external beam irradiation, and all patients were placed on suppressive thyroid hormone therapy. The mean length of follow-up was 19.3 years (range, 1-45 years). RESULTS: Regional recurrent disease developed in 2 patients (15%). No patient experienced the development of worsening pulmonary disease or extra-pulmonary metastases. All patients with recurrent disease underwent selective nodal resections. No patient died of metastatic PTC. Seven patients (50%) remain completely free of disease and are probably cured; 7 patients (50%) are asymptomatic with residual pulmonary disease. CONCLUSIONS: A stepwise treatment approach allows long-term survival and frequent cure for young patients with PTC and concomitant pulmonary metastases.

Noninsulinoma pancreatogenous hypoglycemia syndrome: an update in 10 surgically treated patients.

BACKGROUND: Neuroglycopenia from endogenous hyperinsulinism usually is caused by insulinomas in adults. We recently reported a novel hypoglycemic disorder in 5 patients (patients 1 to 5) with postprandial neuroglycopenia, negative 72-hour fasts, negative perioperative imaging studies, but positive calcium stimulation tests and islet hypertrophy and nesidioblastosis in the gradient-guided resected pancreata. METHODS: In this report we compare our experience with 5 additional patients (patients 6 to 10) with this syndrome to that in the original report. RESULTS: The clinical features of patients 6 to 10 were similar to those of patients 1 to 5. Each had positive calcium stimulation testing that guided the extent of the distal pancreatectomy and histologic evidence of islet cell hypertrophy or nesidioblastosis. All 10 patients are alive from 9 to 50 months after operation, 1 of whom had no amelioration of neuroglycopenia. Minor perioperative complications occurred in 3 patients. One patient has experienced repeated bouts of acute pancreatitis, pseudocyst formation, and exocrine insufficiency. CONCLUSIONS: We have identified adult patients with severe, postprandial hyperinsulinemic hypoglycemia from diffuse islet cell disease, 80% of whom have been well palliated with surgery. The results in 7 men have been better than those in the 3 women for reasons that are not obvious.

Is calciphylaxis best treated surgically or medically?

BACKGROUND: Calciphylaxis is a rare, painful, life-threatening problem of cutaneous necrosis and refractory healing in patients with uremia and secondary hyperparathyroidism. The pathogenesis involves abnormalities in calcium and phosphorus metabolism and acute deposition of calcium in tissues. METHOD: The clinical course of 16 patients who were diagnosed with calciphylaxis at our institution from 1994 through 1998 was reviewed. RESULTS: Fourteen female patients and 2 male patients had chronic renal disease, secondary hyperparathyroidism, and characteristic skin necrosis (mean age, 56 years; range, 39-70 years). All patients underwent intensive medical therapy, including ongoing hemodialysis (n = 16 patients), parathyroidectomy (n = 7 patients), and debridement of cutaneous lesions (n = 8 patients). Mean serum values in surgical and nonsurgical patients were significantly different for phosphorus, calcium-phosphorus product, and parathormone levels. Median survival was 9.4 months; 15 patients (93%) have died. The median survival time for parathyroidectomy versus nonparathyroidectomy was 14.8 and 6.3 months (P =.22), for skin debridement versus nondebridement was 14.1 and 6.1 months (P =.08), and for diabetic versus nondiabetic patients was 6.5 and 13.9 months (P =.11). CONCLUSIONS: Calciphylaxis has a female preponderance, with a dismal prognosis. A multidisciplinary approach that uses frequent hemodialysis to normalize calcium and phosphorus levels and local debridement of skin lesions seems prudent. Parathyroidectomy cannot be recommended routinely in all patients, unless severe hyperparathyroidism mandates intervention.

Gastrointestinal carcinoid tumors: long-term prognosis for surgically treated patients.

To evaluate long-term survival of patients with gastrointestinal carcinoid tumors and to assess factors that may influence prognosis, 154 patients (49% females, 51% males), median age 62 years (range 12-84 years) treated at our institution during 1972-1982 have been followed long term. Tumor location included the foregut (7%), midgut (62%), and hindgut (30%). Ninety-five percent of the patients underwent surgical or endoscopic excision of the primary tumor, with overall operative mortality and postoperative morbidity rates of 2. 6% and 11%, respectively. At follow-up, 60 patients (39%) were alive (median follow-up 18 years; range 1-26 years). The main causes of death included carcinoid tumor burden (32%), unrelated causes (45%), other malignancy (19%), and unknown causes (4%). Observed overall 5- and 10-year survivals were 69% and 53%, respectively. Survival was not related to gender or symptoms at presentation. However, age, embryologic origin, tumor size, depth of invasion, nodal status, and stage of disease proved to be of statistical significance (log-rank). In a multivariate Cox' model, only older age (> 62 years) [P = 0. 001, odds ratio (OR) = 3.4) and embryologic origin (midgut versus foregut) (P = 0.045, OR = 0.45) provided independent prognostic power when death from any cause was taken as the end-point. This study confirms that patient's age and the site of the primary tumor have prognostic significance. Carcinoid tumors are neuroendocrine tumors with a relatively good prognosis, and long-term survival is possible despite advanced stages of disease.

Are patients with multiple endocrine neoplasia type I prone to premature death?

Multiple 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.

What prognostic factors are important in duodenal adenocarcinoma?

HYPOTHESIS: Survival of patients with adenocarcinoma of the duodenum depends on the ability to perform a complete resection and the tumor stage DESIGN: Retrospective case series. SETTING: Tertiary care referral center. PATIENTS: A cohort of 101 consecutive patients (mean age, 62 years), undergoing surgery for duodenal adenocarcinoma from January 1, 1976, through December 31, 1996. Patients with ampullary carcinoma were specifically excluded. Mean duration of follow-up was 4 years. INTERVENTIONS: Surgery was curative in 68 patients (67%) and palliative in 33 patients (33%). Of the curative group, 50 patients (74%) underwent radical surgery, ie, 30 (60%), pancreaticoduodenectomy; 15 (30%), pylorus-preserving pancreaticoduodenectomy; and 5 (10%), total pancreatectomy. A more limited resection procedure was used in 18 patients (26%) involving a segmental duodenal resection in 15 (83%) and a transduodenal excision in 3 (17%). patient survival, and correlation with patient and tumor variables using univariate and multivariate analysis. RESULTS: Actuarial 5-year survival for the curative group was 54%. Only 1 patient in the unresected group survived beyond 3 years. Nodal metastasis (P = .002), advanced tumor stage (P<.001), positive resection margin (P = .02), and weight loss (P<.001) had a significant negative impact on survival in multivariate analysis. Tumor grade, size, and location within the duodenum had no impact on survival. Patient age and tumor depth of invasion influenced survival in univariate analysis, but lost their prognostic significance in multivariate analysis. CONCLUSIONS: Metastasis to lymph nodes, advanced tumor stage, and positive resection margins are associated with decreased survival in patients with duodenal adenocarcinoma. An aggressive surgical approach that achieves complete tumor resection with negative margins should be pursued. Pancreaticoduodenectomy is usually required for cancers of the first and second portion of the duodenum. Segmental resection may be appropriate for selected patients, especially for tumors of the distal duodenum.