Effect on endometrial histology and pharmacokinetics of different dose regimens of progesterone vaginal pessaries, in comparison with progesterone vaginal gel and placebo.

STUDY QUESTION: Which progesterone vaginal pessary dose regimen induces adequate secretory transformation of the endometrium, in comparison with progesterone vaginal gel and placebo? SUMMARY ANSWER: The best secretory transformation of the endometrium was observed during treatment with 400 mg progesterone vaginal pessaries, administered twice daily. WHAT IS KNOWN ALREADY: Vaginally administered progesterone is widely used for luteal phase support (LPS) in assisted reproductive techniques (ART). Although several vaginal formulations using various doses are available, little is known on the impact of formulation and doses at the endometrial level. STUDY DESIGN, SIZE, DURATION: The study had a randomised, observer-blind design and comprised two parts. The participants used study medication during two or three treatment periods, separated by washout periods. Subjects in Part 1 (n = 61 treated) received 200 mg progesterone vaginal pessaries twice daily (bid), 400 mg pessaries bid and the comparator 90 mg progesterone vaginal gel once daily (od) in a 3-way crossover design. Subjects in Part 2 (n = 64 treated) received 100 mg pessaries bid in one period and 400 mg pessaries od in the other period in a 2-way crossover design. A subgroup of these subjects (n = 22 treated) received placebo vaginal pessaries bid in a third period in a non-randomised manner. The study was performed from May 2012 until April 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was performed at a clinical research centre in healthy female volunteers of reproductive age. The subjects used 2 mg estradiol bid for 24 days in each treatment cycle. Progesterone or placebo was administered vaginally from Day 15 onwards during 10 days. In each treatment period, an endometrial biopsy for histological evaluation was performed on Day 23 and pharmacokinetic parameters were determined after the first progesterone dose on Day 15 and after the last dose on Day 24. MAIN RESULTS AND THE ROLE OF CHANCE: Frequencies of (early and late) secretory transformation of the endometrium, i.e. adequate responses, during treatment with 200 mg and 400 mg vaginal pessaries bid were comparable with those during 90 mg vaginal gel treatment (90-94%), whereas lower secretory transformation rates were observed during treatment with 100 mg bid and 400 mg od (64-75%). At the time of the endometrial biopsy in the cycle the late secretory state of the endometrium, which is characteristic of adequate luteal support, was observed more often with 400 mg pessaries bid (90%) than with vaginal gel (82%) and with lower pessary doses (64-78%). Pharmacokinetic parameters after repeated dosing of vaginal pessaries showed a dose-dependent, but not dose-proportional, increase of plasma progesterone levels. The lowest incidence of bleeding and spotting was reported during treatment with 400 mg pessaries bid. LIMITATIONS REASONS FOR CAUTION: The primary outcome parameter, rate of secretory transformation of the endometrium, is a surrogate for endometrial receptivity and for the actual clinical efficacy. WIDER IMPLICATIONS OF THE FINDINGS: Delivery of progestesterone through 400 mg pessaries bid is an effective alternative method for luteal support in ART. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Actavis Group PTC ehf., Iceland, part of Teva Pharmaceuticals, and L.D. Collins. I.D. and C.K. are directors of Dinox, a contract research organisation. I.K. is Managing Director of Pharmaplex and M.W. is Managing Director of M.A.R.C.O., service organisations involved in organisation/supervision and evaluation/reporting of clinical trials. All received funding for the conduct of the study from Actavis. S.H. and Th.M. are employees of Actavis. TRIAL REGISTRATION NUMBER: EudraCT number 2012-001726-95.

Reactive oxygen species mediate high glucose-induced heparanase-1 production and heparan sulphate proteoglycan degradation in human and rat endothelial cells: a potential role in the pathogenesis of atherosclerosis.

AIMS/HYPOTHESIS: The content of heparan sulphate is reduced in the endothelium under hyperglycaemic conditions and may contribute to the pathogenesis of atherosclerosis. Heparanase-1 (HPR1) specifically degrades heparan sulphate proteoglycans. We therefore sought to determine whether: (1) heparan sulphate reduction in endothelial cells is due to increased HPR1 production through increased reactive oxygen species (ROS) production; and (2) HPR1 production is increased in vivo in endothelial cells under hyperglycaemic and/or atherosclerotic conditions. METHODS: HPR1 mRNA and protein levels in endothelial cells were analysed by RT-PCR and Western blot or HPR1 enzymatic activity assay, respectively. Cell surface heparan sulphate levels were analysed by FACS. HPR1 in the artery from control rats and a rat model of diabetes, and from patients under hyperglycaemic and/or atherosclerotic conditions was immunohistochemically examined. RESULTS: High-glucose-induced HPR1 production and heparan sulphate degradation in three human endothelial cell lines, both of which were blocked by ROS scavengers, glutathione and N-acetylcysteine. Exogenous H(2)O(2) induced HPR1 production, subsequently leading to decreased cell surface heparan sulphate levels. HPR1 content was significantly increased in endothelial cells in the arterial walls of a rat model of diabetes. Clinical studies revealed that HPR1 production was increased in endothelial cells under hyperglycaemic conditions, and in endothelial cells and macrophages in atherosclerotic lesions. CONCLUSIONS/INTERPRETATION: Hyperglycaemia induces HPR1 production and heparan sulphate degradation in endothelial cells through ROS. HPR1 production is increased in endothelial cells from a rat model of diabetes, and in macrophages in the atherosclerotic lesions of diabetic and non-diabetic patients. Increased HPR1 production may contribute to the pathogenesis and progression of atherosclerosis.

Elimination of breast tumor-associated chondroitin sulfate promotes metastasis.

Breast cancer is one of the leading causes of cancer-related deaths amongst women in the USA. The tumor microenvironment has been suggested to be an attractive therapeutic target for treatment of cancers. The glycosaminoglycan chondroitin sulfate, as part of the cellular microenvironment, consists of long linear chains of repeating disaccharide units, which are covalently attached to core proteins to form chondroitin sulfate-proteoglycans. In vitro studies have implicated chondroitin sulfate in various aspects of carcinogenesis, whereas the in vivo roles of chondroitin sulfate are less clear. Drastically elevated levels of chondroitin sulfate have been observed within the stromal compartment of many solid tumors, including human breast carcinomas, the significance of which is unknown. We examined the role of tumor-associated chondroitin sulfate in breast cancer progression. Enzymatic elimination of endogenous chondroitin sulfate by intra-tumor injections of chondroitinase ABC leads to the development of secondary tumors and increased lung metastases, while primary orthotopic tumor growth was not affected. These results establish a metastasis-inhibiting effect of primary breast tumor-associated chondroitin sulfate, which may open novel carbohydrate-based therapeutic strategies to combat breast cancer.

Analysis of large versus small pheochromocytomas: operative approaches and patient outcomes.

BACKGROUND: Laparoscopic adrenalectomy for small pheochromocytomas, although challenging, is widely accepted. However, its application to pheochromocytomas larger than 6 cm is questioned due to concerns of malignancy and case complexity. Our aim was to examine the impact of pheochromocytoma tumor size (>/=6 cm vs <6 cm) on operative approach and postoperative patient outcomes. METHODS: A retrospective review of adrenalectomies performed at 3 university hospitals over 1 decade was analyzed. All pheochromocytomas were identified and then divided based on size into large (>/=6 cm) and small (<6 cm) groups. We examined patient and tumor demographics, pathologic diagnosis, operative approach (laparoscopic vs open), postoperative complications, and biochemical cure rates. Data were analyzed using the Student t test and Fisher exact test with a P value <.05 considered significant. RESULTS: From 1995 to 2005, 65 pheochromocytomas were resected. Of the total, 38% (n = 25) tumors were >/=6 cm and 62% (n = 40) were <6 cm. For the large tumors, 1 out of 25 (4%) was malignant, whereas no small tumors were malignant. There was no statistically significant increased risk of malignancy in tumors >/=6 cm in size (P = .31). Initial operative approach was based on surgeon preference. Of the adrenalectomies performed, 88% were laparoscopic, with 3 of 25 (12%) large tumors requiring conversion from laparoscopic to open for intraoperative bleeding. None of the small tumors required conversion. No major postoperative complications (eg, stroke or myocardial infarction) occurred in either group. Minor complications (eg, wound infections and hematomas) were noted in 16% of large tumors and 12.5% of small tumors (P = .45). A total of 96% (24 of 25) patients with large tumors and 100% with small tumors showed postoperative biochemical cure. Tumor recurrence was noted in 1 patient with a tumor <6 cm. CONCLUSIONS: Pheochromocytomas >/=6 cm pose a challenge for laparoscopic resection, and concerns have been raised about the validity of this operative approach. This study demonstrates that there is no significant difference in the rate of malignancy for pheochromocytomas >/=6 cm versus <6 cm. There also were no significant differences identified in complication rates, postoperative biochemical cures, or tumor recurrence rates between these groups. Laparoscopic resection of pheochromocytomas can be safely accomplished regardless of size in centers with surgeons experienced in these procedures.

Improvement in the health-related quality-of-life symptoms of hyperparathyroidism is durable on long-term follow-up.

BACKGROUND: Subjective symptoms such as decreased energy, chronic fatigue, and depression are associated with hyperparathyroidism. Studies have shown that these symptoms are improved during short-term follow-up after parathyroidectomy. This study evaluates the durability of this subjective improvement in quality-of-life symptoms in a large population of patients with follow-up greater than 1 year after operation. METHODS: Between 2002 and 2005, 258 patients underwent parathyroidectomy, 100 (81 females and 19 males) of whom were available for this study. The patients were evaluated with a survey based on the Health Outcomes Institute Health Status Questionnaire. Some answers were quantified on a 1 to 6 scale, while others consisted of "yes" or "no" responses. Patients completed a questionnaire prior to parathyroidectomy and postoperatively at 1 month, 3 to 6 months, and 1 to 2 years or greater intervals. Statistical analysis was used to detect changes attributable to parathyroidectomy. A P value <.05 was considered statistically significant. RESULTS: At 1-month follow-up, patients' perceptions of their overall health, energy level, and mood significantly improved. At 6-month follow-up, significant improvements in muscle strength, health, endurance, and relief of anxiety were documented. At the interval of 1 to 2 years, overall health, energy level, endurance, and relief of anxiety were improved. There was no significant decrement in the quality of life in these patients after parathyroidectomy. CONCLUSIONS: Parathyroidectomy for hyperparathyroidism is associated with significant lasting improvement in subjective symptoms. The potential durable improvement in these quality-of-life symptoms is a valid indication for parathyroidectomy.

Effect of lectins on the metabolism of sulfated glycosaminolycans in cultured fibroblasts.

A short exposure of human skin fibroblasts to Concanavalin A and wheat germ agglutinin led to an intra- and extracellular accumulation of sulfated glycosaminoglycans. The intracellular accumulation was caused by an impaired degradation of sulfated glycosaminoglycans. The increase of extracellular and cell surface associated 35S-labeled proteoglycans could be ascribed to a lectin-mediated inhibition of endocytosis of these polysaccharides. Results obtained with mono- and divalent Concanavalin A derivatives were in agreement with the view that lectins inhibit endocytosis of sulfated proteoglycans by binding to the cell surface receptors specific for these polysaccharides. Proteoglycans secreted by fibroblasts formed precipitable complexes with Concanavalin A. Complex formation reduced markedly the uptake of the proteoglycan. All effects on glycosaminoglycan metabolism mediated by Concanavalin A and wheat germ agglutinin could be prevented by methyl alpha-D-mannoside and N-acetylglucoseamine, respectively.

Metabolism of sulfated glycosaminoglycans in rat hepatocytes. Synthesis of heparan sulfate and distribution into cellular and extracellular pools.

Primary cultures of rat hepatocytes grown in a serum-free medium supplemented with [35S]sulfate synthesize 35S-labelled glycosaminoglycans at an almost constant rate for 58 h. Approx. 57% of the newly synthesized 35S-labelled glycosaminoglycans remain within the hepatocytes, approx. 30% become associated with the cell surface and only 13% are secreted into the medium. The amount of cell-surface-associated 35S-labelled glycosaminoglycans became constant within 36 h, whereas no equilibrium was reached in the intra- and extracellular pool. During a 24 h chase more than 50% of the intracellular and cell-surface-associated 35S-labelled glycosaminoglycans disappears, more than 80% of this material is degraded and radioactivity is recovered as inorganic sulfate. A minor part is released into the medium in a macromolecular form. Heparan sulfate accounts for more than 95% of the 35S-labelled glycosaminoglycans in each of the three pools. It is distinguished from heparan sulfates from other sources by the presence of unsubstituted glucosamine residues. In all three pools, heparan sulfate chains of mean molecular weights between 24 000 and 30 000 are part of an alkali labile proteoglycan. Intra- and extracellularly, however, part of the heparan sulfate appears to have little, if any, protein attached. Hepatocytes contain heparan sulfate-degrading endoglycosidase activity, which may contribute to the variation of molecular weights observed for the heparan sulfate.

Hyperkinetic/aggressive boys in treatment: predictors of clinical response to methylphenidate.

Data on 84 nonretarded boys aged 6--12 with the hyperkinetic/MBD syndrome were drawn from a comprehensive, longitudinal investigation in the interest of identifying factors that contribute significantly to variation in clinically rated improvement during treatment with methylphenidate. The size of the multiple correlation (R = .50) indicates that 25% of the variation in the children's response to methylphenidate is jointly predictable from age at referral, degree of perinatal complications, and score on the hyperactivity factor. The authors discuss stepwise multiple regression analysis as the method of choice in drug response prediction studies and the possible effects on the results of such studies of differing definitions of improvements.

Enhancement of social learning family interventions for childhood conduct disorder.

Social learning family intervention (SLFI) is the treatment of choice for young children exhibiting severe conduct disorder and antisocial behavior. Despite the reported success of this intervention, high levels of resistance, poor engagement, and inadequate maintenance of improvements are observed for a substantial proportion of distressed families. These obstacles have inspired enhancement efforts to improve basic social learning family-intervention models. The present review identifies promising approaches for maximizing treatment gains for the conduct-disordered child. Relevant studies were organized into 3 approaches: enhancements and expansions (a) within a dyadic (parent-child) interaction model, (b) within a broad-based model that acknowledges a wider range of family influences, and (c) through a multisystems model. SLFI enhancements within the dyadic model have centered on either the strengthening of parental skills already included in the SLFI regimen or the adding of new interactional strategies. Some gains, but only partial success, have been achieved with the dyadic model supplements. SLFI expansions from a broad-based model have focused on parental adjustment, parental expectations during treatment, and social-environmental stressors. The multisystems adjuncts to SLFI include cognitive-behavioral interventions to affect peer relations and ecological approaches to sweep across domains. The broad-based and multisystems expansions have produced promising but undertested treatment regimens. Related areas of investigation included therapy process research, medication combined with SLFI, and the involvement of fathers in treatment. Recommendations are offered for improvement of SLFI research. The apparent theoretical crossroads for SLFI treatment of childhood conduct disorder are discussed.

Pheochromocytoma crisis.

Of 26 patients with pheochromocytoma treated between 1974 and 1986, two presented with pheochromocytoma crisis. This unusual presentation consists of hyper- and/or hypotension, high fevers (greater than 40 degrees C), encephalopathy, and multiple organ system failure. Both patients had large tumors associated with markedly elevated levels of epinephrine. Although hypertension was adequately controlled in both patients with phenoxybenzamine, phentolamine (1 patient) and nitroprusside, both patients deteriorated rapidly. The first patient expired during attempts to identify a source of sepsis. None was found at autopsy. The second patient underwent urgent adrenalectomy which reversed the multiple organ system failure and resulted in patient survival. We conclude from review of these patients and three others in the literature that (a) crisis is an unusual presentation of pheochromocytoma; (b) its manifestations include vascular lability, high fever, encephalopathy and multiple organ system failure; (c) it may be the result of increased epinephrine secretion; (d) successful treatment of pheochromocytoma crisis demands prompt diagnosis, vigorous medical therapy and emergent tumor removal if the patient continues to deteriorate.

Adrenalectomy in the era of laparoscopy.

BACKGROUND: Recently laparoscopy has been described as an alternative approach for performing adrenalectomy. This study attempts to define the frequency and indications for the various approaches to adrenalectomy including laparoscopy. METHODS: From October 1992 to December 1995, 43 adrenal glands were excised from 40 patients, of whom 23 were women and 17 were men. Their ages ranged from 16 to 71 years. Nineteen operations were performed for pheochromocytoma, 10 for cortical adenoma (CAd), 6 for aldosteronoma, 4 for adrenocortical cancer (ACC), 1 for Cushing's disease (CD), and 1 for hemorrhagic cyst. Adrenalectomy was accomplished via a laparoscopic operation in 20 patients (8 CAds, 6 pheochromocytomas, 5 aldosteronomas, and 1 HC) and via an open operation in 19 patients (11 pheochromocytomas, 4 ACCs, 2 CAds, 1 CD, and 1 aldosteronoma). One patient with bilateral pheochromocytoma had an open and a laparoscopic adrenalectomy. RESULTS: Open operations included 15 transabdominal, 4 posterior, and 3 thoracoabdominal approaches for 22 glands. Laparoscopic operations included 17 transabdominal and 4 retroperitoneal approaches for 21 glands. Reasons for open operations included obesity (1), patient choice (2), failed laparoscopy (2), previous abdominal surgery (3), extraadrenal location (5); and gland size greater than 8 cm (9). Of these cases, the two patient choices, the two failed laparoscopies, and two of the three previous abdominal operations were appropriate for laparoscopy. Each of the posterior approaches could have been done laparoscopically. CONCLUSIONS: More than 60% of surgically treatable adrenal disease may be approached laparoscopically. Transabdominal, and on occasion, thoracoabdominal approaches are indicated for larger adrenal lesions. Surgeons operating on the adrenal gland should be familiar with each of these various approaches for adrenalectomy.

The effect of somatostatin analogue (SMS 201-995) on pancreatic blood flow.

The effect of somatostatin analogue SMS 201-995 on pancreatic blood flow was studied. In 24 dogs all vessels to the pancreas, except for the pancreaticoduodenal artery and vein, were divided. A flow probe was placed around the pancreaticoduodenal artery. The animals were divided into four groups. Control animals received a subcutaneous injection of 0.5 ml of normal saline solution. Treated animals received 0.002, 0.02, and 0.2 mg/kg of SMS 201-995 at the outset of the experiment. Mean systemic arterial blood pressure, cardiac output, and serum amylase values were monitored, in addition to pancreaticoduodenal blood flow. SMS 201-995 produced a prompt and sustained decrease in pancreatic blood flow in all treated groups compared with control animals without alteration of systemic hemodynamics. This suggests that SMS 201-995 decreases local vascular resistance, which results in decreased pancreatic blood flow.

Calcified pancreatic pseudocysts.

Extensive calcification of a pancreatic pseudocyst that permits visualization on plain abdominal radiographs is unusual. When such x-ray findings are encountered, a broad differential diagnosis can be made, which includes tumors, cysts, abscesses, or malformations of the adjacent structures. Two cases of calcified pancreatic pseudocysts are discussed. Calcified pancreatic pseudocysts may be a potential source of complications such as pain, bleeding, or infection. Because the cyst wall is mature and spontaneous resolution is unlikely, proper treatment of calcified pseudocysts consists of timely resection or internal drainage.

Total thyroidectomy for benign thyroid disease.

BACKGROUND: The goal of this study was to evaluate the safety and efficacy of total thyroidectomy performed for benign thyroid disease. METHODS: A total of 106 consecutive patients undergoing total thyroidectomy for benign disease from October 1982 to July 1995 were reviewed. The 33 men and 73 women had an average age of 46 years (range, 16 to 82 years). Indications for total thyroidectomy were a thyroid nodule with the history of head and neck radiation in 36 patients, bilateral thyroid nodules in 35, needle biopsy of a follicular neoplasm or frozen section diagnosis of a possible malignancy in 18, and toxic goiter in 17. Total thyroidectomy was performed as the primary operation in 98 patients, and 8 patients had a completion reoperation for recurrent disease. RESULTS: Pathology findings revealed benign nodular goiter in 49 patients, follicular adenoma in 26, hyperplasia in 19, and Hashimoto's thyroiditis in 12. Postoperative hemorrhage requiring operative hemostasis occurred in two patients (1.9%). Two patients had unilateral recurrent laryngeal nerve (RLN) palsy before operation (1.9%). Three patients had unilateral postoperative RLN palsy (2.8%). Two cases resolved in 3 and 4 months. The only permanent RLN injury occurred in a patient reoperated for a compressive goiter. Early postoperative hypocalcemia (8.0 mg/dl or less) was found in nine patients (8.5%). No patient had permanent hypoparathyroidism at long-term follow-up evaluation. CONCLUSIONS: Total thyroidectomy for benign thyroid disease can avoid reoperation for nodular goiter and hyperthyroidism and eliminate any subsequent risk of malignant change in radiated thyroid glands. A low complication rate can be achieved with meticulous surgical technique. Total thyroidectomy can be performed safely for bilateral benign thyroid disease.

Androgen receptors in human thyroid tissue.

To evaluate the potential effect of androgens on human thyroid tumors, the incidence and distribution of cytosolic receptors for androgens were analyzed in thyroidectomy specimens from 31 patients. Fourteen specimens were from male and 17 from female patients. The specimens included five papillary carcinomas, five follicular adenomas, 15 colloid goiters, and six relatively normal thyroid tissues. All assays were performed by a protamine sulfate precipitation technique and analyzed by the method of Scatchard. Selected specimens were analyzed by sucrose density gradient. A receptor content greater than 1 fmol/mg cytosol protein was taken as positive if the dissociation constant was less than 1 nm. Seventeen of 31 specimens were positive for androgen receptors, with a dissociation constant of 0.26 +/- 0.09 X 10(-10) M and a receptor content of 11.20 +/- 4.77 fmol/mg cytosol protein. Four of five carcinomas, four of five adenomas, and nine of 21 benign thyroid tissues were positive for androgens. These androgen receptors are a single class with high affinity that are saturable and precipitate at the 6S (Svedberg unit) region similar to receptors in other androgen-dependent tissue. The data suggest that physiologic androgenic milieu may influence the growth of thyroid tumors.

Normalization of intraoperative parathyroid hormone does not predict normal postoperative parathyroid hormone levels.

BACKGROUND: Intraoperative intact parathyroid hormone (iPTH) is being used to confirm complete excision of hyperfunctioning parathyroid tissue. It is uncertain whether normalization of intraoperative iPTH levels accurately predicts long-term postoperative iPTH values. METHODS: Fifty-two consecutive patients with primary or secondary hyperparathyroidism underwent parathyroidectomy with measurement of intraoperative iPTH. Ten patients were excluded due to incomplete laboratory follow-up. Follow-up serum calcium and iPTH levels were measured at 1- and 3-month intervals. RESULTS: Before operation, the mean serum iPTH level was 249 pg/mL (SD=208) and mean serum calcium level was 11.4 +/- 0.9 mg/dL (+/- SD). In all but 4 patients, final intraoperative iPTH levels normalized to less than 67 +/- 41 pg/mL (mean, 35 pg/mL). One week after operation, serum calcium levels had returned to normal (mean, 9.4 +/- 1.1 pg/mL), which directly correlated with the final intraoperative serum iPTH values (Pearson correlation, r = -.434; P <.01). By 1 month, all but 2 patients were normocalcemic (mean, 9.4 +/- 0.9 pg/mL) with a mean iPTH level of 74.8 +/- 82 pg/mL. There was no correlation between final intraoperative and postoperative serum iPTH values (r =.099; P <.533). Both patients with persistent hypercalcemia at 1 month had appropriate intraoperative decreases in iPTH values. CONCLUSIONS: Intraoperative serum iPTH levels significantly correlate with postoperative serum calcium levels but not with postoperative serum iPTH levels. There was a 4.8% failure rate in the correction of postoperative serum calcium levels and a 29% failure rate in the normalization of postoperative serum iPTH levels.

Intraoperative sestamibi scanning in reoperative parathyroidectomy.

BACKGROUND: Reoperative neck exploration for hyperparathyroidism is often difficult even for experienced surgeons. Recent advances in preoperative and intraoperative localization techniques have improved successful resection rates. This prospective study evaluates the accuracy and clinical utility of intraoperative technetium 99m sestamibi scanning for localizing hyperfunctioning parathyroid tissue in reoperative neck explorations. PATIENTS AND METHODS: Eleven patients underwent reoperative neck exploration for hyperparathyroidism. Two patients had 3 prior neck explorations, 1 had 2 prior neck explorations, and 8 patients had 1 prior neck operation. Preoperative studies included sestamibi scintigraphy and ultrasound in all patients, magnetic resonance imaging in 4, computed tomography scan in 3, parathyroid arteriogram in 1, and selective venous sampling in 1. All patients underwent intraoperative technetium 99m sestamibi scanning and parathyroid hormone assay. RESULTS: Preoperative technetium 99m sestamibi scanning and ultrasound each successfully localized 7 of 11 hyperfunctioning glands (64%). Intraoperative technetium 99m sestamibi scanning correctly localized 10 of 11 hyperfunctioning glands (91%). Intraoperative parathyroid hormone assay confirmed successful excision of hyperfunctioning tissue in all 11 patients. Postoperatively, all 11 patients had low-normal or normal calcium levels. CONCLUSIONS: Intraoperative technetium 99m sestamibi correctly localized 91% of hyperfunctioning glands compared with 64% localization for preoperative technetium 99m sestamibi and preoperative ultrasound. Intraoperative technetium 99m sestamibi scanning and parathyroid hormone monitoring are useful in reoperative neck explorations for hyperparathyroidism.

Effect of failed computed tomography-guided and endoscopic drainage on pancreatic pseudocyst management.

BACKGROUND: Computed tomography and endoscopic drainage are used increasingly to treat pancreatic pseudocysts (PP). We reviewed our experience with PP to compare the outcomes of patients operated on initially (group 1) with those whose nonoperative treatment failed (computed tomography-guided or endoscopic drainage) before operation (group 2). METHODS: The records of 70 consecutive patients operated on for PP were reviewed. The 52 patients (74%) in group 1 and 18 (26%) in group 2 were compared in terms of clinical features, laboratory test results on examination and before operation, operative findings, morbidity, mortality, and recurrence rates. RESULTS: Before the initial drainage attempt, mean serum amylase level was higher in group 2 (542 +/- 25 vs 163 +/- 17 IU/L; p = 0.01). All other laboratory values were similar. Before operative drainage, group 2 patients had lower hemoglobin (10.7 +/- 0.5 vs 12.2 +/- 0.3 gm/dl; p < 0.05) and serum albumin level (2.7 +/- 0.2 vs 3.5 +/- 0.1 mg/dl; p < 0.01) than group 1. Morbidity was twice as frequent in group 2 (33% vs 14%). The time from initial attempt at drainage to PP resolution was longer in group 2 (104 +/- 36 vs 20 +/- 4 days; p = 0.01). However, the time from operation to resolution was similar in both groups (21 +/- 8 vs 20 +/- 4 days). CONCLUSIONS: Failed nonoperative drainage is associated with a protracted illness and carries a risk of increased morbidity after operative intervention.

Are cystgastrostomy and cystjejunostomy equivalent operations for pancreatic pseudocysts?

To compare the effectiveness of cystgastrostomy and cystjejunostomy for treatment of pancreatic pseudocysts, 39 patients with cystgastrostomy were compared to 59 patients with cystjejunostomy. The groups were comparable in age, sex, cause of pancreatitis, pseudocyst location, symptoms, and preoperative serum amylase level. Cysts treated with cystgastrostomy were larger (mean diameter, 11.1 +/- 0.9 cm) than cysts treated by cystjejunostomy (mean diameter, 6.7 +/- 0.7 cm) (p less than 0.05). Mean duration of surgery was 148 +/- 11 minutes for cystgastrostomy versus 265 +/- 15 minutes for cystjejunostomy (p less than 0.05). Mean blood loss was 397 +/- 82 ml for cystgastrostomy versus 703 +/- 80 ml for cystjejunostomy (p less than 0.05) Mean intraoperative fluid requirements were 2640 +/- 313 ml for cystgastrostomy and 4403 +/- 362 ml for cystjejunostomy (p less than 0.05). Cyst recurrence was 10% for cystgastrostomy versus 7% for cystgastrostomy. Postoperative gastrointestinal bleeding occurred in 8% of patients with cystgastrostomy and in 2% of patients with cystjejunostomy. Infection problems with cystjejunostomy included two wound infections and one case of septicemia; infection problems with cystjejunostomy included five intraabdominal abscesses, two wound infections, and one case of pneumonia. Two patients died with cystgastrostomy (both from gastrointestinal bleeding); two patients died with cystjejunostomy (one from intraabdominal sepsis and one from pulmonary embolus). Cystgastrostomy was used for significantly larger pseudocysts and was associated with significantly less blood loss and operating time than cystjejunostomy (p less than 0.05). Morbidity and mortality from cystgastrostomy and cystjejunostomy were comparable, although gastrointestinal bleeding was more common with cystgastrostomy and intraabdominal abscess was more common with cystjejunostomy. Since cystgastrostomy can usually be performed more quickly and with less blood loss, it should be considered whenever anatomically feasible.