Value of 18-Fluorodeoxyglucose Positron Emission Tomography in the Management of Patients With Cystic Tumors of the Pancreas

OBJECTIVE: To assess the reliability of 18-fluorodeoxyglucose positron emission tomography (18-FDG PET) in distinguishing benign from malignant cystic lesions of the pancreas. SUMMARY BACKGROUND DATA: The preoperative differential diagnosis of cystic lesions of the pancreas remains difficult: the most important point is to identify malignant or premalignant cysts that require resection. 18-FDG PET is a new imaging procedure based on the increased glucose metabolism by tumor cells and has been proposed for the diagnosis and staging of pancreatic cancer. METHODS: During a 4-year period, 56 patients with a suspected cystic tumor of the pancreas underwent 18-FDG PET in addition to computed tomography scanning, serum CA 19-9 assay, and in some instances magnetic resonance imaging or endoscopic retrograde cholangiopancreatography. The 18-FDG PET was analyzed visually and semiquantitatively using the standard uptake value. The accuracy of 18-FDG PET and computed tomography was determined for preoperative diagnosis of a malignant cyst. RESULTS: Seventeen patients had malignant tumors. Sixteen patients (94%) showed 18-FDG uptake with a standard uptake value of 2.6 to 12.0. Twelve patients (70%) were correctly identified as having malignancy by computed tomography, CA 19-9 assay, or both. Thirty-nine patients had benign tumors: only one mucinous cystadenoma showed increased 18-FDG uptake (standard uptake value 2.6). Five patients with benign cysts showed computed tomography findings of malignancy. Sensitivity, specificity, and positive and negative predictive values for 18-FDG PET and computed tomography scanning in detecting malignant tumors were 94%, 97%, 94%, and 97% and 65%, 87%, 69%, and 85%, respectively. CONCLUSIONS: 18-FDG PET is more accurate than computed tomography in identifying malignant pancreatic cystic lesions and should be used, in combination with computed tomography and tumor markers assay, in the preoperative evaluation of patients with pancreatic cystic lesions. A positive result on 18-FDG PET strongly suggests malignancy and, therefore, a need for resection; a negative result shows a benign tumor that may be treated with limited resection or, in selected high-risk patients, with biopsy, follow-up, or both.     

Treatment of Frey's syndrome with botulinum toxin type B

Objective

Frey's syndrome is a frequent sequela of parotidectomy, causing facial sweating and flushing because of gustatory stimuli. Although botulinum toxin type A has become first-line therapy for Frey's syndrome, some patients become resistant. In this study, we investigated whether another serotype, botulinum toxin type B, might be an effective alternative.

Study Design

Case series with planned data collection.

Setting

Otolaryngology department in a university hospital.

Subjects and Methods

Seven patients aged 30 to 68 years, with severe Frey's syndrome, underwent the Minor test and had 80 U of botulinum toxin type B per cm² (mean total dose, 2354 U) injected intracutaneously in the mapped area of gustatory sweating. All patients were followed up for 12 months.

Results

One month after treatment, six of the seven patients reported that gustatory sweating and flushing had resolved, and, in the remaining patient, these symptoms had decreased. The Minor test confirmed a significant improvement. The subjective benefits remained stable for six months in four patients and for nine months in the remaining three patients; 12 months after treatment, all patients still reported some improvement.

Conclusion

Botulinum toxin type B afforded symptomatic relief in a small sample of patients with Frey's syndrome and might be considered a potential alternative to botulinum toxin type A.     

Baseline observations from the POSSIBLE EU® study: characteristics of postmenopausal women receiving bone loss medications

Summary

Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) is an ongoing longitudinal cohort study that utilises physician- and patient-reported measures to describe the characteristics and management of postmenopausal women on bone loss therapies. We report the study design and baseline characteristics of 3,402 women recruited from general practice across five European countries.

Purpose

The POSSIBLE EU® is a study describing the characteristics and management of postmenopausal women receiving bone loss medications.

Methods

Between 2005 and 2008, general practitioners enrolled postmenopausal women initiating, switching or continuing treatment with bone loss treatment in France, Germany, Italy, Spain and the UK. Patients and physicians completed questionnaires at study entry and at 3-month intervals, for 1 year.

Results

Of 3,402 women enrolled (mean age 68.2 years [SD] 9.83), 96% were diagnosed with low bone mass; 55% of these using dual energy X-ray absorptiometry. Most women (92%) had comorbidities. Mean minimum T score (hip or spine) at diagnosis was ?2.7 (SD 0.89; median ?2.7 [interquartile range, ?3.2, ?2.2]) indicating low bone mineral density. Almost 40% of the women had prior fractures in adulthood, mostly non-vertebral, non-hip in nature, 30% of whom had at least two fractures and more than half experienced moderate/severe pain or fatigue. Bisphosphonates were the most common type of bone loss treatment prescribed in the 12 months preceding the study.

Conclusions

POSSIBLE EU® characterises postmenopausal women with low bone mass, exhibiting a high rate of prevalent fracture, substantial bone fragility and overall comorbidity burden. Clinical strategies for managing osteoporosis in this population varied across the five participating European countries, reflecting their different guidelines, regulations and standards of care.     

Predictors of mortality and management of patients with traumatic inferior vena cava injuries

The aim of this study was to determine factors that predict mortality in patients with traumatic inferior vena cava (IVC) injuries and to review the current management of this lethal injury. A 7-year retrospective review of all trauma patients with IVC injuries was performed. Factors associated with mortality were assessed by univariate analysis. Significant variables were included in a multivariate regression analysis model to determine independent predictors of mortality. Statistical significance was determined at P < or = 0.05. A literature review of traumatic IVC injuries was performed and compared with our institutional experience. Thirty-six IVC injuries were identified (mortality, 56%; mechanisms of injury, 28% blunt and 72% penetrating). There was no difference in mortality based on mechanism of injury. Injuries with closer proximity to the heart were associated with increased mortality (P < 0.001). Univariate analysis demonstrated that nonsurvivors had a higher injury severity scale, a lower systolic blood pressure in the emergency department, a lower Glasgow coma score (GCS), and were more likely to have thoracotomies performed in the emergency department or operating room. Multivariate analysis revealed that only GCS (P = 0.03) was an independent predictor of mortality. Typical factors predicting mortality were identified in our cohort of patients, including GCS. The mechanism of injury is not associated with survival outcome, although mortality is higher with injuries more proximal to the heart. The form of management by IVC level is reviewed in our patient population and compared with the literature.     

Effect of endothelin receptor antagonist on parathyroid gland growth, PTH values and cell proliferation in azotemic rats.

BACKGROUND: A variety of stimuli are involved in the pathogenesis of parathyroid gland hyperplasia in renal failure. Recently, it was shown that blocking the signal from the endothelin-1 (ET-1) receptor (ET(A)R/ET(B)R) by a non-selective receptor antagonist, bosentan, reduced parathyroid cell proliferation, parathyroid gland hyperplasia and parathyroid hormone (PTH) levels in normal rats on a calcium deficient diet. Our goal was to determine whether in 5/6 nephrectomized (NPX) rats with developing or established hyperparathyroidism, the endothelin receptor blocker, bosentan, reduced the increase in parathyroid cell proliferation, parathyroid gland hyperplasia and PTH values. METHODS: High (HPD, 1.2%) or normal phosphorus diets (PD) (NPD, 0.6%) were given to 5/6 NPX rats for 15 days (NPX(15)). In each dietary group, one-half the rats were given bosentan (B) i.p. 100 mg/kg/day. The four groups of rats were: (1) NPX(15)-1.2% P; (2) NPX(15)-1.2% P+B; (3) NPX(15)-0.6% P; and (4) NPX(15)-0.6% P+B. In a second study in which hyperparathyroidism was already established in 5/6 NPX rats fed a HPD for 15 days, rats were divided into two groups in which one group was maintained on a HPD and the other group was changed to very low PD (VLPD, <0.05%) for an additional 15 days. In each dietary group, one-half the rats were given bosentan i.p. 100 mg/kg-day. The four groups of rats were: (1) NPX(30)-1.2% P; (2) NPX(30)-1.2% P+B; (3) NPX(30)-0.05% P and (4) NPX(30)-0.05% P+B. Parathyroid cell proliferation was measured by proliferating cell nuclear antigen (PCNA) staining and ET-1 expression by immunohistochemical techniques. RESULTS: In the study of developing hyperparathyroidism, bosentan reduced ET-1 expression in the parathyroid glands of rats on the NPD and HPD (P<0.05). But only in rats on the NPD did bosentan result in a reduced increase in parathyroid gland weight (P<0.05). In the study of established hyperparathyroidism, in which 5/6 NPX rats were given a HPD for 15 days, bosentan started on day 15 reduced (P<0.05) ET-1 expression in rats maintained for 15 additional days on the HPD or the VLPD. On the VLPD, parathyroid gland weight was less (P<0.05) than that in rats on the HPD sacrificed at 15 or 30 days. Bosentan did not reduce parathyroid cell proliferation or parathyroid gland weight in rats maintained on the HPD or further reduce these parameters beyond that obtained with dietary phosphorus restriction. PTH values were lowest in the VLPD group, intermediate in the NPD group, and highest in the HPD group, but in none of the three groups did bosentan decrease PTH values. CONCLUSIONS: In azotemic rats with developing hyperparathyroidism, bosentan resulted in a reduced increase in parathyroid gland weight when dietary phosphorus content was normal. Despite a reduction in ET-1 expression in rats on a HPD with developing or established hyperparathyroidism, bosentan did not reduce the increase in parathyroid cell proliferation, parathyroid gland growth or PTH values. Thus, ET-1 blockade with bosentan did not prevent parathyroid gland growth in the azotemic rat.     

Outcome of Portal Injuries Following Bariatric Operations

Background: Portal vein thrombosis is rare following Roux-en-Y gastric bypass (RYGBP). Its natural history is dependent on the etiology of the thrombosis. Iatrogenic injuries at bariatric operations resulting in portal vein thrombosis are lethal complications typically necessitating a liver transplant, whereas postoperative portal vein thrombosis without an injury to the portal vein has a benign course. There are currently no data on management or prognostic factors of portal vein thrombosis after bariatric operations. Methods: 3 patients referred for liver transplantation secondary to portal vein injury following bariatric surgery between 2000 and 2003 are presented. Results: 2 super-obese (BMI ≥50 kg/m²) and 1 morbidly obese (BMI 44 kg/m²) patients sustained portal vein injuries during bariatric surgery (RYGBP 2, VBG 1) by experienced bariatric surgeons. In each case, the portal injury was identified and repaired. Thrombosis followed reconstruction in all 3 patients. All 3 underwent emergency liver transplantation, but died of sepsis and multi-organ failure following transplantation. Review of the literature found no cases of traumatic portal vein injuries following bariatric operations and 2 cases of postoperative portal vein thrombosis: 1 following LRYGBP (BMI 46) and one after a Lap-Band (BMI 41). Conclusion: Injury to the portal vein resulting from difficulty in discerning the anatomy of the intra-abdominal structures in the morbidly obese, is a lethal complication of bariatric surgery. Super-obese patients submitting to bariatic surgery should lose weight, undergo a two-stage bariatric procedure, or undergo laparoscopic RYGBP to minimize the risk of portal injury. Postoperative portal vein thrombosis has a benign course and can be managed conservatively.     

V-region mutation in vitro,in vivo,and in silico reveal the importance of the enzymatic properties of AID and the sequence environment

The somatic hypermutation of Ig variable regions requires the activity of activation-induced cytidine deaminase (AID) which has previously been shown to preferentially deaminate WRC (W = A/T, R = A/G) motif hot spots in in vivo and in vitro assays. We compared mutation profiles of in vitro assays for the 3′ flanking intron of VhJ558-Jh4 region to previously reported in vivo profiles for the same region in the Msh2^−/−Ung^−/− mice that lack base excision and mismatch repair. We found that the in vitro and in vivo mutation profiles were highly correlated for the top (nontranscribed) strand, while for the bottom (transcribed) strand the correlation is far lower. We used an in silico model of AID activity to elucidate the relative importance of motif targeting in vivo. We found that the mutation process entails substantial complexity beyond motif targeting, a large part of which is captured in vitro. To elucidate the contribution of the sequence environment to the observed differences between the top and bottom strands, we analyzed intermutational distances. The bottom strand shows an approximately exponential distribution of distances in vivo and in vitro, as expected from a null model. However, the top strand deviates strongly from this distribution in that mutations approximately 50 nucleotides apart are greatly reduced, again both in vivo and in vitro, illustrating an important strand asymmetry. While we have confirmed that AID targeting of hot and cold spots is a key part of the mutation process, our results suggest that the sequence environment plays an equally important role.