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.

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.

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy.

AIMS/HYPOTHESIS: Recent studies suggest that loss of heparan sulphate in the glomerular basement membrane (GBM) of the kidney with diabetic nephropathy is due to the increased production of heparanase, a heparan sulphate-degrading endoglycosidase. Our present study addresses whether heparan sulphate with different modifications is differentially reduced in the GBM and whether heparanase selectively cleaves heparan sulphate with different domain specificities. METHODS: The heparan sulphate content of renal biopsies (14 diabetic nephropathy, five normal) were analysed by immunofluorescence staining with four anti-heparan sulphate antibodies: JM403, a monoclonal antibody (mAb) recognising N-unsubstituted glucosamine residues; two phage display-derived single chain antibodies HS4C3 and EW3D10, defining sulphated heparan sulphate domains; and anti-K5 antibody, an mAb recognising unmodified heparan sulphate domains. RESULTS: We found that modified heparan sulphate domains (JM403, HS4C3 and EW3D10), but not unmodified domains (anti-K5) and agrin core protein were reduced in the GBM of kidneys from patients with diabetic nephropathy, compared with controls. Glomerular heparanase levels were increased in diabetic nephropathy kidneys and inversely correlated with the amounts of modified heparan sulphate domains. Increased heparanase production and loss of JM403 staining in the GBM correlated with the severity of proteinuria. Loss of modified heparan sulphate in the GBM as a result of degradation by heparanase was confirmed by heparan sulphate staining of heparanase-treated normal kidney biopsy specimens. CONCLUSIONS/INTERPRETATION: Our data suggest that loss of modified heparan sulphate in the GBM is mediated by an increased heparanase presence and may play a role in the pathogenesis of diabetes-induced proteinuria.

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.

Health-related quality of life in hyperparathyroidism measurably improves after parathyroidectomy.

BACKGROUND: Hyperparathyroidism is associated with subjective feelings of fatigue and depression as well as limitations in physical activity from musculoskeletal complaints. These quality of life symptoms are not widely accepted as an indication for parathyroidectomy. This study quantifies and compares subjective symptoms of patients with hyperparathyroidism before and after surgery. METHODS: Between February 2001 and June 2002, 61 patients (14 males and 47 females, mean age of 60.8+/-14.4 years) underwent parathyroidectomy. There were 45 patients with single-gland adenomas, 9 patients with double adenomas, 3 patients with primary hyperparathyroidism from 4-gland hyperplasia, 3 patients with secondary hyperparathyroidism, and 1 patient with tertiary hyperparathyroidism. Patients filled out a 53-question survey based on the Health Outcomes Institute Health Status Questionnaire 2.0 before surgery, 1 month postoperatively, and 3-24 months postoperatively. The survey included questions on overall health, daily activities, mood, and medical conditions. Surveys were analyzed for changes in symptoms attributable to parathyroidectomy. Serum calcium and intact parathyroid hormone levels were obtained preoperatively and at 1- and 3-month follow-up visits. RESULTS: At both postoperative evaluations, patients' perception of general health, muscle strength, energy level, and mood significantly improved (P<.05). Moreover, there was a significant correlation between the changes in serum calcium and intact parathyroid hormone levels and improvement in symptoms. CONCLUSIONS: Parathyroidectomy for hyperparathyroidism is associated with significant improvement in patient quality of life. These subjective symptoms represent a valid indication for parathyroidectomy.

Experimental chronic entrapment of the sciatic nerve in adult hamsters: an ultrastructural and morphometric study

Entrapment neuropathy is a group of clinical disorders involving compression of a peripheral nerve and interference with nerve function mostly through traction injury. We have investigated the chronic compression of peripheral nerves as an experimental procedure for detecting changes in ultrastructural nerve morphology. Adult hamsters (Mesocricetus auratus, N = 30) were anesthetized with a 25 percent pentobarbital solution and received a cuff around the right sciatic nerve. Left sciatic nerves were not operated (control group). Animals survived for varying times (up to 15 weeks), after which they were sacrificed and both sciatic nerves were immediately fixed with a paraformaldehyde solution. Experimental nerves were divided into segments based upon their distance from the site of compression (proximal, entrapment and distal). Semithin and ultrathin sections were obtained and examined by light and electron microscopy. Ultrastructural changes were qualitatively described and data from semithin sections were morphometrically analyzed both in control and in compressed nerves. We observed endoneurial edema along with both perineurial and endoneurial thickening and also the existence of whorled cell-sparse structures (Renaut bodies) in the subperineurial space of compressed sciatic nerves. Morphometric analyses of myelinated axons at the compression sites displayed a remarkable increase in the number of small axons (up to 60 percent) in comparison with the control axonal number. The distal segment of compressed nerves presented a distinct decrease in axon number (up to 40 percent) comparatively to the control group. The present experimental model of nerve entrapment in adult hamsters was shown to promote consistent histopathologic alterations analogous to those found in chronic compressive neuropathies

Insulinoma presenting with hyperandrogenism: a case report and a literature review.

An 18-year-old woman presented with a 6-month history of amenorrhoea and hyperandrogenism. Three months later she developed several episodes of fasting hypoglycaemia and was subsequently diagnosed with an insulinoma. Hyperinsulinaemia was observed in association with an elevated serum testosterone level. Surgical removal of the insulinoma resulted in resolution of the clinical and biochemical features of the polycystic ovarian syndrome (PCOS). Polycystic ovarian syndrome is unusual in a patient having an insulinoma. The rarity of this association may be the result of the late age of onset of this type of tumour, intermittent secretion of excessive insulin by the tumour, the degree of hyperinsulinism or other factors extrinsic to the insulin receptor that may facilitate insulin activity. However, we could not discover how our patient differs in having had PCOS from the majority of women with insulinoma who do not. If other patients with insulinoma are subsequently found to have hyperandrogenism, then this tumour might be added to the differential diagnosis of causes of anovulatory cycles and hyperandrogenaemia, although rare the association would be uncommon.

Intraocular metastases: differential diagnosis from uveal melanomas with high-resolution MRI using a surface coil.

Magnetic resonance imaging with dedicated surface coils plays a pivotal role in differential diagnosis and staging of intraocular tumors. The purpose of this study was to establish MRI criteria for the differential diagnosis of uveal melanomas and intraocular metastases. In a prospective study 44 eyes in 36 patients with intraocular metastases and 200 patients with uveal melanomas were investigated with MRI using a 1.5-T scanner and a 5-cm surface coil. Both quantitative and qualitative evaluation of the resulting images was performed. The MR signal intensities typically expected for metastases (slightly hyperintense on non-contrast T1-weighted images and hypointense on T2-weighted images compared to the vitreous body) were seen in only 23.1%. The typical melanoma signal of either moderate or strong hyperintensity on T1-weighted images and hypointensity on T2-weighted images was seen in 69.4% of the proven melanomas. Contrast enhancement was observed in both metastases and melanomas. Morphological differences between metastases and melanomas were detected in tumor size, shape, position, frequency of retinal detachment, and homogeneity of the tumor. Differentiation between intraocular metastases and uveal melanoma is limited by overlap of signal intensities. Some improvement is achieved with morphologic criteria.

The effect of glucagon-like peptide 2 on intestinal permeability and bacterial translocation in acute necrotizing pancreatitis.

BACKGROUND: Acute pancreatitis (AP) initiates a generalized inflammatory response that increases intestinal permeability and promotes bacterial translocation (BT). Impairment of the intestinal epithelial barrier is known to promote BT. Glucagon-like peptide 2 (GLP-2), a 33 residue peptide hormone, is a key regulator of the intestinal mucosa by stimulating epithelial growth. The purpose of this study was to determine whether GLP-2 decreases intestinal permeability and BT in AP. METHODS: To examine whether GLP-2 can decrease intestinal permeability and thereby decrease BT in acute necrotizing pancreatitis, 34 male Sprague-Dawley rats (200 to 300 g) were studied. AP was induced in group I and group II by pressure injection of 3% taurocholate and trypsin into the common biliopancreatic duct (1 mg/kg of body weight). The potent analog to GLP-2 called ALX-0600 was utilized. Group I rats received GLP-2 analog (0.1 mg/kg, SQ, BID) and group II rats received a similar volume of normal saline as a placebo postoperatively for 3 days. Group III and group IV received GLP-2 analog and placebo, respectively. At 72 hours postoperatively, blood was drawn for culture of gram-negative organisms. Specimens from mesenteric lymph nodes (MLN), pancreas and peritoneum were harvested for culture of gram-negative bacteria. Intestinal resistance as defined by Ohm's law was determined using a modified Ussing chamber to measure transepithelial current at a fixed voltage. A point scoring system for five histologic features that include intestinal edema, inflammatory cellular infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to evaluate the severity of pancreatitis. Specimens from MLN, pancreas, jejunum, and ileum were taken for pathology. RESULTS: All group I and group II rats had AP. The average transepithelial resistance in group I was 82.8 Omega/cm(2) compared with 55.9 Omega/cm(2) in group II (P <0.01). Gram-negative BT to MLN, pancreas, and peritoneum was 80%, 0%, and 0%, respectively in group I compared with 100%, 30%, and 20% translocation in group II. CONCLUSION: GLP-2 treatment significantly decreases intestinal permeability in acute pancreatitis.

Use of intraoperative parathyroid hormone measurement does not improve success of bilateral neck exploration for hyperparathyroidism.

HYPOTHESIS: Use of intraoperative measurement of intact parathyroid hormone (iPTH) to confirm complete excision of hyperfunctioning parathyroid tissue does not improve overall operative success rates. DESIGN: Case series of patients undergoing parathyroidectomy with or without intraoperative iPTH measurement. SETTING: University teaching hospital. PATIENTS AND INTERVENTIONS: Fifty patients undergoing parathyroidectomy before our institution of intraoperative iPTH sampling in March 1999 (group 1) were compared with 50 patients undergoing parathyroidectomy after this technique was adopted (group 2). Overall, 100 patients underwent operation between December 1996 and May 2000. Serum calcium and iPTH levels were measured at 1- and 3-month intervals. Intraoperative frozen sections and operative times were also analyzed. RESULTS: Mean preoperative calcium levels were 2.85 and 2.82 mmol/L (11.4 and 11.3 mg/dL) in groups 1 and 2, respectively. One-month postoperative calcium values were identical in both groups at 2.35 mmol/L (9.4 mg/dL) (group 1 SD = 0.18 [0.74], group 2 SD = 0.20 [0.82]). At 1 month, all but 1 patient in group 1 had normalized calcium values (2% failure rate), while 3 patients in group 2 (6%) remained hypercalcemic. All 3 patients in group 2 had intraoperative iPTH levels that returned to normal. There was a significant difference in the number of intraoperative frozen sections between groups, with a mean (SD) of 3.4 (1.7) in group 1 and 2.0 (1.6) in group 2 (P<.01). There was no significant difference in operative times between groups. CONCLUSIONS: Use of intraoperative iPTH sampling did not significantly affect the overall success of parathyroidectomy, as determined by postoperative normocalcemia. There was, however, a significant decrease in the number of frozen sections sent at operation.

Pancreatic epithelial cyst in an adult treated by central pancreatectomy.

The infrequent occurrence of benign epithelial cysts of the pancreas is the reason why little is known regarding their clinical relevance and surgical management. We report the case of a 38-year-old woman with a benign epithelial cyst that was resected by the rarely performed central pancreatectomy. The presentation, evaluation, and differences between this and other cystic lesions of the pancreas are discussed. The benefits of central pancreatectomy for this benign lesion are reviewed.

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.

The effect of interleukin-6 on bacterial translocation in acute canine pancreatitis.

BACKGROUND: Bacterial translocation from the gut to mesenteric lymph nodes and other extraintestinal sites is an important source of infection in acute pancreatitis. Impaired host immunity is known to promote bacterial translocation. Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase reaction, and hematopoiesis. METHODS: Twenty-four mongrel dogs (18-29 kg) were studied in four equal groups. In Groups I and II, acute pancreatitis was induced by direct pressure injection of 4% taurocholate and trypsin into the pancreatic duct at laparotomy. Groups III and IV had only laparotomy. Group I and III dogs were given IL-6 (50 microg/kg/d, sq) daily starting 24 h after operation and Group II and IV dogs received an equal volume of saline administered at similar time. All animals had blood drawn for culture, complete blood count (CBC), platelets, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and amylase on d 0, 1, 4, and 7. On d 7, mesenteric lymph nodes (MLN), spleen, liver, pancreas, and cecum were harvested for pathology study and for cultures of aerobic and anaerobic bacteria. Quantitative cecal cultures of aerobic and anaerobic bacteria were obtained. RESULTS: All Group I and Group II dogs had severe pancreatitis. The increase of plasma CRP in Group I was sustained throughout treatment (1.3+/-0.3 on d 0 vs 3.1+/-0.3*, 3.0+/-0.3*, and 2.9+/-0.3* on d 1,4, and 7, respectively). Plasma CRP was increased in Group II on d 1 and d 4 (1.3+/-0.3 mg/dL on d 0 vs 3.6+/-0.3* mg/dL on d 1, and 3.1+/-0.3* on d 4, *p < 0.05). There were no differences in white blood cell (WBC) count, differential, platelets, and ESR between Groups I and II. Bacterial translocation to MLN was lower in Group I (1/6) than in Group II (6/6) (p < 0.05). All 6 dogs in Group II had bacterial spread to distant sites compared to 2 of 6 dogs in Group I (p = 0.066). Both MLN and other distant organ cultures were negative in Group III and only 1 of 6 MLN cultures was positive in Group IV. CONCLUSIONS: IL-6 treatment decreases bacterial translocation to MLN and may be beneficial in reducing septic complications in acute pancreatitis.

The role of positron emission tomography in selecting patients with metastatic cancer for adrenalectomy.

Metastases to the adrenal glands usually signal disseminated disease. However, isolated metastases do occur that may be curable with adrenalectomy. Functional imaging with positron emission tomography (PET) can differentiate benign from malignant pathology and isolated from disseminated metastases. The purpose of this study was to determine whether PET scanning can influence the outcome of adrenalectomy for metastatic disease. We conducted a retrospective review of eight patients undergoing adrenalectomy for presumed isolated metastatic disease from 1985 through 1997. The patients included six women and two men with an average age of 58 (range, 36-74). Their primary tumors were six lung carcinomas, one renal cell carcinoma, and one colon carcinoma. The adrenal masses were located on the right in six patients, on the left in one, and bilaterally in one. Before operation, all patients were evaluated by chest and abdominal CT. Four patients were also evaluated by PET scan. Six right, one left, and one bilateral adrenalectomies were performed. Associated organ resections included two right partial nephrectomies and one right total nephrectomy, one left partial nephrectomy, two distal pancreatectomies, one splenectomy, and two partial hepatic resections. All eight patients survived operation. There were no major perioperative complications, but one patient required readmission for congestive heart failure. Three of the four patients who did not have PET scanning died from 4 to 48 months after operation with disseminated disease from lung, colon, and renal carcinoma respectively. The remaining patient who did not have PET scanning is alive and well 11 years later. Two of the four patients who had PET scans showing isolated disease are alive at 28 and 43 months after operation, whereas the other two died of disseminated disease at 29 and 36 months after operation. We conclude that 1) adrenalectomy can provide survival benefit in patients with isolated metastases, and 2) PET scanning is useful in confirming isolated metastatic disease and selecting patients for adrenalectomy.