Citations

AbstractAmiodarone‐associated thyrotoxicosis (AAT) is often poorly tolerated owing to underlying cardiac disease, and it is frequently refractory to conventional medical treatment. The goal of this study was to describe the patient characteristics, management, and outcomes of all the patients treated surgically for AAT at a single institution. We conducted a retrospective chart review of all patients managed surgically for AAT (April 1985 through November 2002) at the Mayo Clinic in Rochester, Minnesota. Altogether, 29 men and 5 women, ages 39 to 85 years (median 60 years), treated with amiodarone for 3 to 108 months underwent near‐total or total thyroidectomy. Frequent symptoms were worsening heart failure, fatigue, weight loss, and tremor. Altogether, 12 patients failed medical management of their AAT, and 21 received no preoperative medical therapy. One patient had been successfully managed medically but required definitive treatment. Common indications for operation were the need to remain on amiodarone, cardiac decompensation, medically refractory disease, and severe symptoms, both hyperthyroid and cardiac, necessitating prompt resolution. The median ± SD American Society of Anesthesiologists (ASA) classification (1 = healthy through 5 = moribund) was 3.00 ± 0.58. A total of 27 specimens had histology consistent with AAT. Complications included death (n = 3), rehospitalization (n = 3), symptomatic hypocalcemia (n = 2), pneumonia (n = 2), cervical hematoma (n = 1), prolonged ventilatory wean (n = 1), and stroke (n = 1); one patient developed hypotension, adult respiratory distress syndrome, and sepsis. Of the 31 surviving patients, 25 (80%) remained on amiodarone postoperatively. The median follow‐up was 29 months, at which time all surviving patients were free of hyperthyroid symptoms. Thyroidectomy is an effective treatment for AAT but has a high incidence of perioperative morbidity and mortality. The cardiovascular co‐morbidities and high operative risk in this group of patients may account for the increased complication rate.

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.

Purpose This multicenter, open-label, phase II study was undertaken to assess the antitumor activity and safety of the oral mitogen-activated extracellular signal regulated kinase kinase (MEK) inhibitor, CI-1040, in breast cancer, colon cancer, non-small-cell lung cancer (NSCLC), and pancreatic cancer. Patients and Methods Patients with advanced colorectal, NSCLC, breast, or pancreatic cancer received oral CI-1040 continuously at 800 mg bid. All patients had measurable disease at baseline, a performance status of 2 or less, and adequate bone marrow, liver, and renal function. Expression of pERK, pAkt, and Ki-67 was assessed in archived tumor specimens by quantitative immunohistochemistry. Results Sixty-seven patients with breast (n = 14), colon (n = 20), NSCLC (n = 18), and pancreatic (n = 15) cancer received a total of 194 courses of treatment (median, 2.0 courses; range, one to 14 courses). No complete or partial responses were observed. Stable disease (SD) lasting a median of 4.4 months (range, 4 to 18 months) was confirmed in eight patients (one breast, two colon, two pancreas, and three NSCLC patients). Treatment was well tolerated, with 81% of patients experiencing toxicities of grade 2 or less severity. Most common toxicities included diarrhea, nausea, asthenia, and rash. A mild association (P < .055) between baseline pERK expression in archived tumor specimens and SD was observed. Conclusion CI-1040 was generally well tolerated but demonstrated insufficient antitumor activity to warrant further development in the four tumors tested. PD 0325901, a second generation MEK inhibitor, has recently entered clinical development and, with significantly improved pharmacologic and pharmaceutical properties compared with CI-1040, it may better test the therapeutic potential of MEK inhibition in cancer.

Cluster headache is the most severe of the primary headaches. Positron emission tomography and functional MRI studies have shown that the ipsilateral posterior hypothalamus is activated during cluster headache attacks and is structurally asymmetric in these patients. These changes are highly specific for the condition and suggest that the cluster headache generator may be located in that brain area; they further suggest that electrical stimulation of that region might produce clinical improvement in chronic cluster headache sufferers refractory to medical therapy. In five patients with severe intractable chronic cluster headache, hypothalamic electrical stimulation produced complete and long-term pain relief with no relevant side-effects. We therefore consider it essential to propose criteria for selecting chronic cluster headache patients for hypothalamic deep brain stimulation before this procedure is undertaken at other academic medical centres.

Background— The incidence, determinants, and outcome of postoperative atrial fibrillation (AF) after surgery for mitral regurgitation (MR) are poorly defined but may have important implications for timing of mitral valve surgery. Methods and Results— In 762 patients in sinus rhythm with no AF history undergoing MR surgical correction, we examined the rates and prognostic implications of postoperative AF for early AF (within 2 weeks postoperatively) and late AF (>2 weeks after surgery). During postoperative follow-up, 180 patients (24%) experienced new AF (early AF in 136 and late AF in 111). Isolated early AF without recurrence was observed in 69 patients characterized by high angina class and lower left ventricular ejection fraction but no significant left atrial (LA) enlargement. However, overall early AF predicted late AF: 62±5% of patients with early AF had late AF at 10 years compared with 9±1% of patients without early AF ( P <0.0001). Large LA size strongly and independently predicted early AF ( P =0.01) and late AF ( P =0.003). For late AF, the predictive value of an enlarged LA was cumulative to that of early AF. Postoperative AF was associated with an increased subsequently higher risk of stroke or congestive heart failure (adjusted risk ratio=1.46 [1.04 to 2.05], P =0.03). Conclusions— Postoperative AF is common after surgical correction of MR in patients with no prior history of AF and is associated with increased subsequent morbidity. LA enlargement is independently predictive of postoperative AF and as such, should be integrated into the clinical decision-making process in patients with MR.

AbstractAlthough useful palliation can often be achieved when external beam irradiation and chemotherapy are used to treat locally advanced gastrointestinal malignancies, local control and long‐term survival are infrequent in view of the limited tolerance of surrounding organs and tissues. In view of dose limitations of external beam irradiation, intraoperative irradiation (IORT) with electrons has been used as a supplement to external treatment in an attempt to improve the therapeutic ratio of local control versus complications. An IORT dose of 10 to 20 Gy has been combined with fractionated external beam doses of 45 to 55 Gy in 1.8 Gy fractions in studies performed in the United States, Japan, Europe, and Scandinavian countries. In this paper the indications for and the results of aggressive combined techniques that include IORT are discussed. Results obtained with external beam techniques alone or with chemotherapy and resection are presented by site to demonstrate the need for higher doses of irradiation. When results from IORT series are compared to standard treatment with regard to disease control and survival, local control appears better with locally advanced colorectal, gastric, and pancreatic cancer; and survival appears better with colorectal ± biliary cancers. With pancreatic cancer, improvements in local control do not translate into increased survival in view of the high incidence of subsequent liver and peritoneal failures. Implications for future strategies in all sites are discussed.

AbstractOur aim was to examine the long‐term success of cholecystoenterostomy performed for the relief of benign extrahepatic biliary obstruction. Concern about the ability of cholecystoenterostomy to provide reliable long‐term biliary decompression has led many to abandon its use for benign biliary obstruction. Thirty‐four patients who underwent cholecystoenterostomy for benign biliary obstruction over a 17‐year period were reviewed. Patients were followed until cholecystoenterostomy failure, death, or to date. Failure was defined as recurrent biliary obstruction or cholangitis requiring therapeutic intervention. Mean follow‐up was 8.0 years. Early postoperative morbidity occurred in 11 patients (32%), but only one early complication (cholangitis) was related directly to the cholecystoenteric anastomosis. Five patients (15%) experienced late biliary tract complications related directly to the cholecystoenterostomy including recurrent biliary stones with biliary obstruction in four and anastomotic stricture in one. All required reoperation and conversion to choledochoenterostomy at a mean of 112 months. Cholecystoenterostomy can provide reasonably effective long‐term biliary decompression in selected patients with benign biliary obstruction.