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Hip fractures usually occur in elderly patients who commonly have pre-existing medical problems or comorbidities. We retrospectively reviewed 100 patients admitted to our unit with a hip fracture to quantify their medical complexity. Age and comorbidity profile were used to determine an age-adjusted Charlson Co-morbidity Index (ACCI). The findings were then compared to 100 patients admitted under the care of the acute medical team. The patients in the fracture group were significantly older (p<0.0001), had significantly more co-morbidities (p<0.0001) and had a significantly greater predicted one-year mortality (p<0.0001). Cardiorespiratory disorders were the most common co-morbidities in the hip fracture group. We discuss our findings in combination with a review of the pertinent literature., Competing Interests: Provenance: externally peer-reviewed., (Copyright © 2019 Ulster Medical Society.)

Introduction: Collagenase Clostridium Histolyticum (CCH) is a recognised treatment option for adult patients presenting with Dupuytren's contracture (DC)., Patients and Methods: Twenty male patients with established DC were treated using CCH. The average metacarpophalangeal (MCP) joint and proximal interphalangeal joint (PIP) contractures pre-treatment were 52 0 (range, 0 - 75 0 ) and 35 0 (range, 0 - 84 0 ) respectively. The average DASH score pre-treatment was 24.2 points (range, 0 - 68.2 points). Patients were reviewed at lmonth, 3months and at an average of 23 months (17 to 27 months)., Results: MCP joint contractures significantly improved compared to pre-treatment and the improvement was maintained at latest follow up. PIP joint contractures did significantly improve but to a lesser degree and there was no significant improvement compared to pre-treatment beyond 3months. A trend for MCP and PIP joint contracture recurrence was observed at latest follow up but did not reach statistical significance. DASH scores significantly improved from pre-treatment and the improvement was maintained at latest follow up. At 3months, the average patient satisfaction score was 9.5 (range, 6 - 10), which decreased to 8.6 (range, 6 - 10) at latest follow up. We estimated a potential cost saving of approximately £70,000 by treating 20 patients using CCH compared to inpatient operative fasciectomy., Conclusion: CCH is a useful option in the management of DC in appropriately selected patients. Cost-effectiveness in the treatment of DC should be carefully considered., Competing Interests: Provenance: externally peer-reviewed.

Introduction: Acute kidney injury (AKI) is a common but preventable cause of morbidity in elective arthroplasty patients. This study aimed to review the incidence and management of AKI in patients undergoing elective lower limb arthroplasty and compare results to those after the introduction of educational measures to improve prevention, recognition and management of AKI., Methods: A retrospective case note review of all patients undergoing elective hip or knee arthroplasty between August and October 2013 was performed. Results were compared to patients treated from February to April 2014, after the introduction of a renal protection protocol, checklist poster and educational sessions. Results were statistically compared using Fisher's exact test., Results: Two hundred and eleven patients were included in the study: 104 in the initial cohort and 107 in the second cohort. Twenty patients (19.2 %) developed AKI in the initial cohort and 12 patients (11.2 %) in the second (p = 0.13). Recognition, documentation and management of AKI were significantly better following educational sessions and dissemination of posters throughout clinical areas, with 75 % of patients in the second cohort having their AKI documented and treated versus 30 % in the initial cohort., Discussion/conclusions: This quality improvement project has demonstrated the significant impact that simple educational measures can have on improving AKI prevention, recognition and management in patients undergoing elective arthroplasty surgery. The introduction of a logical treatment checklist has been well received by both medical and nursing staff and ensures prompt and efficient management of AKI in a non-specialist area.

Introduction: In April 2011 the NI public health agency estimated that alcohol misuse generates overall annual healthcare costs of £122.2m. There is currently a paucity of data regarding the burden of alcohol-related fractures on the provinces Trauma and Orthopaedic service., Patients and Methods: A retrospective review of 104 patients over a 12 month period was performed. Data collected using the Fractures Outcomes and Research Database included: age, gender, smoking status, weekly alcohol intake, mechanism of injury and subsequent treatment., Results: Alcohol related fractures accounted for 6.1% of all acute fractures admissions in the 12 month period. 73% were male, with a bimodal age distribution. The majority of patients were classed as social drinkers; however a significant proportion (23.1%) were alcohol dependent. 62.5% of patients were smokers at the time of admission. 95% of patients suffered a single injury which was commonly secondary to a simple mechanical fall (53.8%). The majority of patients sustained lower limb injuries, with 30.8% of these being ankle fractures., Conclusion: In conclusion, our study has identified that alcohol-related trauma creates a significant financial burden on the NHS. It is likely that the incidence of alcohol related fracture is higher than documented in this study. We advocate the assessment of patients using the AUDIT-C score to assess for at risk drinking behaviour in those presenting with an alcohol related fracture.

Background: The purpose of this study is to describe outcomes of MEN-1 patients with recurrence requiring completion pancreatectomy and duodenectomy after initial treatment of pancreatic endocrine neoplasms (PENs) and hypergastrinemia with distal pancreatectomy, enucleation of pancreatic head PENs, and duodenotomy., Methods: After undergoing this initial operation, 8 of 49 patients (16%) have required completion pancreatectomy and duodenectomy for recurrent PENs and hypergastrinemia. Retrospective review was performed., Results: Median age was 39 years (27-51) at completion pancreatectomy compared to 31 years (20-40) at initial operation. Pathology revealed multiple PENs in 100%, duodenal neoplasms in 63%, and metastatic lymph nodes in 75%. There was no operative mortality and 88% of patients are currently alive. Preoperative gastrin levels were 934 +/- 847 pg/mL while postoperative levels are 93 +/- 79 pg/mL (normal 25-111 pg/mL). Mean Hemoglobin A1C levels are 8.3 +/- 3.3% (normal 3.8%-6.4%). Mean follow-up is 44 +/- 25 months., Conclusion: This initial operation may provide tumor control and prevent metastases but recurrent PENs are multifocal and progressive. Completion pancreatectomy and duodenectomy is arduous but outcomes are acceptable. Considering the radical nature of this treatment, individual consideration should be given to MEN-1 patients amenable to initial alternative pancreatic resections that preserve pancreatic mass and allow future pancreas-preserving reoperations.

The aim of this study was to investigate whether a standard course of outpatient physiotherapy improves the range of knee motion after primary total knee arthroplasty. One hundred and fifty patients were randomly assigned into one of 2 groups. One group received outpatient physiotherapy for 6 weeks (group A). Another received no outpatient physiotherapy (group B). Range of knee motion was measured preoperatively and at 1-year review. Validated knee scores and an SF-12 health questionnaire were also recorded. Although patients in group A achieved a greater range of knee motion than those in group B, this was not statistically significant. No difference either was noted in any of the outcome measures used. In conclusion, outpatient physiotherapy does not improve the range of knee motion after primary total knee arthroplasty.

Background: Surgical treatment of primary hyperaldosteronism (PHA) requires demonstration of unilateral adrenal hypersecretion. Optimal methods for interpretation of imaging and invasive testing are still in development., Methods: A retrospective review from 1996-2007 of 106 patients with PHA was undertaken. Patient demographics, biochemical studies, radiologic imaging, operative reports, and pathology were reviewed and comparisons made. Optimal ratios for adrenal vein sampling were tested with regard to sensitivity and specificity. Preoperative and postoperative medication requirements and blood pressures were compared among different treatment groups., Results: Seventy-eight patients (62 surgically treated) met criteria for inclusion. Median arterial blood pressure at diagnosis was 150/86 mm Hg while taking 3 antihypertensive medications. 69.2% required potassium supplementation. Median aldosterone:renin ratio was 107.0. Forty-two AVS procedures changed the management of 15 patients (35.7%) when compared to CT results. AVS accuracy was 96.6 vs 88.9% for NP-59 scintigraphy. Operative patients remained on fewer antihypertensive medications (1 vs 3), and mean systolic pressure was lower (130 vs 146 mm Hg) compared with medically managed patients., Conclusion: When used together, pre-ACTH aldosterone ratios, normalized A/C:A/C ratios, ratios to define contralateral suppression, and post-ACTH stimulated values allowed for capture of episodically secreting tumors and subtle unilateral or bilateral hyperaldosteronism.

We describe the use of a vascularised periosteal patch onlay graft based on the 1,2 intercompartmental supraretinacular artery in the management of 11 patients (ten men, one woman) with chronic nonunion involving the proximal third of the scaphoid. The mean age of the patients was 31 years (21 to 45) with the dominant hand affected in eight. Six of the patients were smokers and three had undergone previous surgery to the scaphoid. All of the proximal fragments were avascular. The presence of union was assessed using longitudinal axis CT. Only three patients progressed to union of the scaphoid and four required a salvage operation for a symptomatic nonunion. The remaining four patients with a persistent nonunion are asymptomatic with low pain scores, good grip strength and a functional range of wrist movement. Although this technique has potential technical advantages over vascularised pedicled bone grafting, the rate of union has been disappointing and we do not recommend it as a method of treatment.

We reviewed the outcomes of 34 patients who had undergone vascularised bone grafting for a chronic scaphoid non-union. Mean age was 27 years (range 16-46 years). The dominant hand was involved in 17 cases. Eleven patients were smokers. In 18 cases the fracture involved the proximal and in 16 cases the middle third of the scaphoid. In 26 patients the proximal scaphoid fragment was deemed avascular. Sixteen patients had previously undergone scaphoid fixation and non-vascularised bone grafting. At a follow-up of 1 to 3 years (mean 1.6 years), 15 of the 34 scaphoid non-unions had united. Injury to the dominant hand and duration of the non-union significantly increased the risk of failure. Persistent non-union was more common in proximal third fractures and in the presence of an avascular proximal pole but these findings did not reach statistical significance.

It is recommended that full-length femoral radiographs should be obtained in patients presenting with a femoral neck fracture and a co-existent history of malignancy. Over a two-year period, we identified 133 (47 males, 86 females) patients admitted with a femoral neck fracture and a co-existent history of malignant disease, representing 6.5% of all femoral neck fractures admitted within this time frame. None of the patients had previously diagnosed bone metastases. The mean patient age was 80 years (range, 30-97 years). In 114 cases the fracture was traumatic in origin, most commonly a simple fall (86%). In 19 cases the fracture was atraumatic with histopathological analysis demonstrating the presence of bony metastases. Overall, breast (35%), lower gastrointestinal (22%), prostatic (18%) and bronchogenic carcinomas (7%) were the most common associated malignancies. On reviewing the full-length anteroposterior and lateral femoral radiographs, none of the patients had demonstrable pathology in the remainder of the femur. Furthermore, none of the patients to date have required readmission with a secondary fracture relating to disease in the middle or distal thirds of their femur. We conclude that full-length views of the femur are of limited value in patients presenting with a femoral neck fracture and a co-existent history of malignant disease.

We report a series of 706 patients (759 hip implants) with an average follow up of 10.5 years (range, 10-11 years) following total hip replacement (THR) using a cemented custom-made femoral stem and a cemented HDP acetabular component. The fate of every implant is known. One hundred and seventy-four patients (23%) were deceased at the time of their 10-year review all died with a functioning THR in situ. Four hundred and sixty-two patients (61%) were subsequently reviewed. One hundred and twenty three patients (16%) were assessed by telephone review, as they were too ill or unwilling to attend. Kaplan-Meier survival analysis (all components) demonstrated a median survival at 10 years of 96.05% or 95% Confidence Intervals (CI) for median survival of (94.41% to 97.22%). Revision surgery occurred in 30 cases (3.9%). Seventeen had full revisions (2.2%) and 13 (1.7%) socket revisions only. Twenty-one out of 30 revisions were for infection or dislocation. There were 2 cases (0.3%) of revision for aseptic loosening of the stem. The 10-year results of the custom femoral titanium stem are encouraging and compare well with other cemented systems.

We have studied the concept of posterior condylar offset and the importance of its restoration on the maximum range of knee flexion after posterior-cruciate-ligament-retaining total knee replacement (TKR). We measured the difference in the posterior condylar offset before and one year after operation in 69 patients who had undergone a primary cruciate-sacrificing mobile bearing TKR by one surgeon using the same implant and a standardised operating technique. In all the patients true pre- and post-operative lateral radiographs had been taken. The mean pre- and post-operative posterior condylar offset was 25.9 mm (21 to 35) and 26.9 mm (21 to 34), respectively. The mean difference in posterior condylar offset was + 1 mm (-6 to +5). The mean pre-operative knee flexion was 111 degrees (62 degrees to 146 degrees) and at one year postoperatively, it was 107 degrees (51 degrees to 137 degrees). There was no statistical correlation between the change in knee flexion and the difference in the posterior condylar offset after TKR (Pearson correlation coefficient r = -0.06, p = 0.69).

Rupture of the tibialis posterior tendon can be missed. We report a case of posterior tibialis tendon rupture that, owing to misdiagnosis, resulted in a significant foot deformity requiring arthrodesis for chronic pain.

Thyroid cancer poses a significant clinical challenge, and our understanding of its pathogenesis is incomplete. To gain insight into the pathogenesis of papillary thyroid carcinoma, transcriptional profiles of four normal thyroids and 51 papillary carcinomas (PCs) were generated using DNA microarrays. The tumors were genotyped for their common activating mutations: BRAF V600E point mutation, RET/PTC1 and 3 rearrangement and point mutations of KRAS, HRAS and NRAS. Principal component analysis based on the entire expression data set separated the PCs into three groups that were found to reflect tumor morphology and mutational status. By combining expression profiles with mutational status, we defined distinct expression profiles for the BRAF, RET/PTC and RAS mutation groups. Using small numbers of genes, a simple classifier was able to classify correctly the mutational status of all 40 tumors with known mutations. One tumor without a detectable mutation was predicted by the classifier to have a RET/PTC rearrangement and was shown to contain one by fluorescence in situ hybridization analysis. Among the mutation-specific expression signatures were genes whose differential expression was a direct consequence of the mutation, as well as genes involved in a variety of biological processes including immune response and signal transduction. Expression of one mutation-specific differentially expressed gene, TPO, was validated at the protein level using immunohistochemistry and tissue arrays containing an independent set of tumors. The results demonstrate that mutational status is the primary determinant of gene expression variation within these tumors, a finding that may have clinical and diagnostic significance and predicts success for therapies designed to prevent the consequences of these mutations.

Acetabular extrusion of cement during total hip arthroplasty is a well-recognised occurrence. We report a case of femoral neuropathy secondary to an extruded cement mass nine years after primary cemented total hip arthroplasty. Removal of the cement resulted in resolution of the patients symptoms. (Hip International 2005; 15: 182-3).

Fas-mediated apoptosis has been proposed to play an important role in the pathogenesis of Hashimoto's thyroiditis. Normal thyroid cells are resistant to Fas-mediated apoptosis in vitro but can be sensitized by the unique combination of interferon-gamma and IL-1beta cytokines. We sought to examine the mechanism of this sensitization and apoptosis signaling in primary human thyroid cells. Without the addition of cytokines, agonist anti-Fas antibody treatment of the thyroid cells resulted in the cleavage of proximal caspases, but this did not lead to the activation of caspase 7 and caspase 3. Apoptosis associated with the cleavage of caspases 7, 3, and Bid, and the activation of mitochondria in response to anti-Fas antibody occurred only after cytokine pretreatment. Cell surface expression of Fas, the cytoplasmic concentrations of procaspases 7, 8, and 10, and the proapoptotic molecule Bid were markedly enhanced by the presence of the cytokines. In contrast, P44/p42 MAPK (Erk) appeared to provide protection from Fas-mediated apoptosis because an MAPK kinase inhibitor (U0126) sensitized thyroid cells to anti-Fas antibody. In conclusion, Fas signaling is blocked in normal thyroid cells at a point after the activation of proximal caspases. Interferon-gamma/IL-1beta pretreatment sensitizes human thyroid cells to Fas-mediated apoptosis in a complex manner that overcomes this blockade through increased expression of cell surface Fas receptor, increases in proapoptotic molecules that result in mitochondrial activation, and late caspase cleavage. This process involves Bcl-2 family proteins and appears to be compatible with type II apoptosis regulation.

Over a 2-year period, 244 patients underwent hemiarthroplasty for a displaced intracapsular femoral neck fracture. Seventy patients had a cementless Austin-Moore prosthesis (AMP) inserted and 174 patients were treated using a cemented Thompson hemiarthroplasty. All the AMPs were inserted by or under the supervision of an orthopaedic consultant. Five patients (7%) from the AMP group sustained a periprosthetic femoral fracture. Two were iatrogenic and three occurred postoperatively after a simple fall. The fractures occurred proximally around the prosthesis (Johansson type I). Four required revision surgery. There were no periprosthetic femoral fractures in the Thompson group. When compared to the cemented Thompson hemiarthroplasties, the number of periprosthetic femoral fractures was significantly greater with the AMP. Patients in the AMP group were significantly older, although there was no significant difference in ASA grade between the two groups. There was no significant difference in age or gender between those who sustained a periprosthetic fracture and those who did not. These findings suggest that due to the increased risk of periprosthetic femoral fracture, cemented hemiarthroplasty is preferable. Furthermore, with modern cementing techniques, elderly frail patients appear to tolerate bone cement, which may serve to reinforce an osteoporotic proximal femur.

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by parathyroid tumours, which are frequently carcinomas, and ossifying jaw fibromas. In addition, some patients may develop renal tumours and cysts. The gene causing HPT-JT, which is referred to as HRPT2 and is located on chromosome 1q31.2, encodes a 531 amino acid protein called PARAFIBROMIN. To date 42 mutations, of which 22 are germline, have been reported and 97% of these are inactivating and consistent with a tumour suppressor role for HRPT2. We have investigated another four HPT-JT families for germline mutations, searched for additional clinical phenotypes, and examined for a genotype-phenotype correlation. Mutations were found in two families. One family had a novel deletional-insertion at codon 669, and the other had a 2 bp insertion at codon 679, which has been reported in four other unrelated patients. These five unrelated patients and their families with the same mutation were not found to develop the same tumours, thereby indicating an absence of a genotype-phenotype correlation. An analysis of 33 HPT-JT kindreds revealed that affected women in 13 HPT-JT families suffered from menorrhagia in their second to fourth decades. This often required hysterectomy, which revealed the presence of uterine tumours. This resulted in a significantly reduced maternal transmission of the disease. Thus, the results of our analysis expand the spectrum of HPT-JT-associated tumours to include uterine tumours, and these may account for the decreased reproductive fitness in females from HPT-JT families.

Background: The management of multiple endocrine neoplasia, type 1 (MEN-1) pancreatoduodenal neuroendocrine neoplasms (NENs) is controversial. An aggressive surgical approach is intended to control the functional syndromes and malignant potential for nodal or distant metastasis., Methods: The results of treating 39 patients with MEN-1 pancreatoduodenal NENs over a 35-year period are available from chart reviews and patient interviews. This study focuses on pattern of disease, disease recurrence, and long-term functional outcomes., Results: Between 1967 and 2003, 39 patients ages 19 to 58 years (mean age, 37) had abdominal operations for their pancreatoduodenal NENs: 26 with Zollinger-Ellison syndrome, 4 with hypoglycemia, 3 with both Zollinger-Ellison syndrome and hypoglycemia, and 6 with nonfunctional neoplasms. Fifteen of these 39 patients had malignant disease on initial abdominal operation; 24 of 39 patients have not required abdominal reoperation, 17 of whom have available follow-up data. Of these 17 patients, 11 have biochemical evidence of disease recurrence (increased serum concentrations of gastrin, insulin, or pancreatic polypeptide), while 6 have no biochemical evidence of recurrence. A total of 30 abdominal reoperations were performed in 15 patients; 14 of 15 patients undergoing 1 or more reoperations developed evident malignant disease by their most recent operation. Nine of 13 reoperative patients with follow-up data have evidence of disease recurrence. Functional outcomes available in 20 patients showed that 10 patients require insulin and that 6 require oral hypoglycemic medications. Ninety percent have no abdominal pain or nausea/vomiting, while 4 are unable to return to work secondary to this disease., Conclusions: Treatment of MEN-1 pancreatoduodenal NENs is met with frequent recurrence and some treatment-related morbidity and mortality. Most patients (22 of 39) eventually demonstrated malignant growth, but, with this strategy, few died of this disease.

Non-union is an uncommon but troublesome complication of proximal humeral fractures. A number of surgical techniques have been reported. We describe the use of a contoured limited-contact dynamic compression plate in the surgical management of proximal humeral non-union.

A retrospective review of 991 primary total hip arthroplasties was performed to determine the incidence of rapidly progressive osteoarthrosis of the hip joint. Thirty-four patients (35 hips) were identified (3.5%). Females were predominantly affected (85%). A history of hypertension and regular non-steroidal anti-inflammatory drug use was significantly more common in those with rapid progression as compared to the normally progressive group. Transfusion requirements were also significantly greater for the rapidly progressive group. Patient age and operating time were both greater in those with rapid progression, but neither proved statistically significant. No significant difference was noted when comparing the affected side, body mass index or the pre-operative range of hip movements, ESR or Oxford Hip Score. From the radiographs, twenty cases were classified as type I (rapid), 11 type II (moderate) and 3 type III (delayed). Wear distribution was predominantly superolateral (85%) and anterosuperior (97%). All patients were treated by total hip arthroplasty. At latest follow-up (average, 18 months; range, 13-36 months) there was no significant difference in the Oxford Hip Score between the normally progressive and rapidly progressive groups. All radiographs were satisfactory. Total hip arthroplasty in these cases is technically challenging. When identified, such individuals should be given priority treatment due to the potentially rapid and extensive loss of bone stock that can occur. (Hip International 2004; 14: 217-22).

From a one-surgeon series of 2485 patients, we report on 10 patients with rotating platform dislocation after primary Low Contact Stress total knee arthroplasty. All dislocations occurred within 2 years of the index procedure. Of the 10 patients, nine required open reduction. Five of these patients also had exchange of the original insert. One patient was treated by closed reduction. All knees were immobilized in a cast for 8 weeks. Eight of the 10 patients had no additional dislocation and at followup (average, 35 months; range, 12 months-5 years), had a stable functional joint. Two patients had recurrent spinout of the rotating platform develop. One patient had arthrodesis whereas the other patient had the insert cemented to the tibial tray as a salvage procedure. Increasing age, a preoperative valgus deformity, and prior patellectomy were significantly associated with rotating platform spinout. Surgical experience and an improved understanding of the soft tissue constraints, particularly in the valgus knee, are important in minimizing this complication.

Enterochromaffin-like (ECL) tumors are documented in patients with hypergastrinemia secondary to chronic atrophic gastritis or with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1 (ZES-MEN-1). In patients with ECL tumors and atrophic gastritis, normogastrinemia after antrectomy has resulted in resolution, regression, or stabilization of ECL tumors. The natural history of ECL tumors associated with ZES-MEN-1 following normalization of gastrin levels after gastrinoma resection has not been previously reported. The purpose of this study was to determine the course of ECL tumors in patients with ZES-MEN-1 following normalization of serum gastrin levels after gastrinoma resection. Two patients with ZES-MEN-1 had biopsy-proven ECL tumors on endoscopic evaluation. They then underwent surgical exploration that included distal pancreatectomy, enucleation of pancreatic head tumors, duodenotomy with excision of submucosal tumors, and peripancreatic lymphadenectomy. Gastric ECL tumors larger than 1.0 cm were locally excised. Patients underwent long-term follow-up with biochemical and endoscopic surveillance. Normogastrinemia was achieved and sustained following gastrinoma resection in two patients with ZES-MEN-1. Periodic endoscopic surveillance over a 6-year period showed complete resolution of the ECL tumors. The development of ECL tumors associated with ZES-MEN-1 is multifactorial. Studies identified a genetic influence on tumor growth with loss of heterozygosity at the MEN-1 gene locus in ECL tumors. The resolution of ECL tumors in ZES-MEN-1 patients who are normogastrinemic indicates that an elevated gastrin level is a primary initiator for development of these tumors. Therefore both genetic defects and hypergastrinemia are causative agents. Normalization of serum gastrin levels is critical for the prevention of aggressive forms of ECL tumors.

Hypothesis: A nomogram based on regression analysis of intraoperative parathyroid hormone level decay discriminates single gland disease from multiglandular (MG) disease more accurately than the currently used 50% rule., Design: Retrospective case series., Setting: Academic health center., Patients: Two hundred thirty-five patients (222 patients with single gland disease and 13 patients with MG disease) who underwent parathyroidectomy., Interventions: Intraoperative parathyroid hormone level analysis at baseline, time 1 (about 5 minutes), and time 2 (about 10 minutes) after excision of the first gland., Main Outcome Measures: The mean slope was calculated at time 1 and time 2 and analyzed using one-way analysis of variance and the Fisher least significance difference post hoc tests using data normalized to baseline intraoperative parathyroid hormone levels to compare patients with single gland disease with patients with MG disease. A regression-based nomogram was created to analyze individual kinetic decay data., Results: The mean (SEM) single gland disease slope was significantly steeper than the MG disease slope at both time 1 (-0.91 [0.02] vs -0.66 [0.05]; P<.01) and time 2 (-0.77 [0.01] vs -0.56 [0.05]; P<.01). When the standard threshold rule of a 50% decrease from baseline was used, only 23% of the patients with MG disease were correctly predicted by intraoperative parathyroid hormone values (77% false-positive result rate) at time 1. However, the nomogram correctly predicted 54% of the patients with MG disease at time 1 (46% false-positive result rate). At time 2, the standard threshold 50%-rule method correctly predicted 38% of the patients with MG disease (62% false-positive result rate), while the nomogram still correctly classified 54% of the patients with MG disease (46% false-positive result rate)., Conclusions: A regression-based nomogram incrementally improves prediction of MG disease compared with the standard 50%-rule method and accounts for variability in the exact timing of samples. Slope analysis suggests that the earliest time point best isolates the kinetics of the excised gland. The nomogram will need to be validated prospectively.

Primary thyroid cells are resistant to TNF-related apoptosis-inducing ligand (TRAIL). Previously we showed that the combination of IL-1beta and TNFalpha facilitated TRAIL-mediated apoptosis in these cells and enhanced cell surface expression of TRAIL receptors. The aim of this study was to further characterize the mechanism by which these cytokines sensitized primary thyroid cells to TRAIL-mediated apoptosis. IL-1beta and TNFalpha increased the concentrations of procaspase-7 and Bid. In contrast, the p44/42 MAPK (Erk) pathway was active in thyroid cells and this activity was significantly decreased after exposure to IL-1beta/TNFalpha. A MAPK kinase inhibitor (U0126) could enhance the cytokine-induced sensitization of thyroid cells to TRAIL, reinforcing the inhibitory role of Erk on TRAIL signaling. In conclusion, IL-1beta/TNFalpha treatment sensitizes human thyroid cells to TRAIL-mediated apoptosis through increased surface expression of TRAIL receptors, increased expression of procaspase-7 and Bid, and the inhibition of p44/42 MAPK (Erk) pathway.

Background: EUS is highly sensitive, specific, and cost-effective for localization of pancreatic neuroendocrine tumors. EUS screening of asymptomatic patients with multiple endocrine neoplasia type 1 has not been described., Methods: EUS was used to evaluate all patients with known or suspected pancreatic neuroendocrine tumors. Asymptomatic patients with either a confirmed genetic or clinical diagnosis of multiple endocrine neoplasia type 1 were evaluated with EUS. The results were correlated with surgical and histopathologic findings., Results: A total of 65 patients with multiple endocrine neoplasia type 1 underwent 132 EUS procedures over an 8-year period, including 13 asymptomatic patients. Five of the 13 asymptomatic patients had normal serum gastrin levels, and 8 had levels less than 4 times the upper limit of normal. EUS demonstrated pancreatic neuroendocrine tumors in 11 of these patients, ranging in size from 0.4 to 4 cm (mean 10 mm). Ten of the 11 patients with tumors at EUS underwent surgical exploration, and 23 of 28 (82%) tumors removed surgically had been identified by EUS. At a mean follow-up of 44 months, no liver or lymph node metastases were demonstrated in any patient., Conclusions: In this first cohort study of asymptomatic patients with multiple endocrine neoplasia type 1 undergoing screening EUS, pancreatic neuroendocrine tumors were identified before the development of significant biochemical test abnormalities. Aggressive early surgical treatment may improve the prognosis for these patients.

Background: Patients with multiple endocrine neoplasia (MEN) type 1 risk premature death from pancreatic endocrine tumours (PETs). Endoscopic ultrasonography (EUS) is the most sensitive imaging modality for small PETs. A screening and therapeutic approach for asymptomatic patients is delineated in which EUS plays a pivotal role., Methods: This was a retrospective study of 15 patients with MEN-1 but with no symptoms of a PET. All patients underwent serum hormone measurement, including gastrin, and EUS. The findings were used to facilitate operative treatment., Results: Six of 15 patients had a normal basal gastrin level and nine had a raised level. EUS demonstrated PETs in 14 patients and identified multiple lesions in 12. There was no predictive relationship between age or gastrin level and the number or size of PETs discovered. Thirteen patients have undergone enucleation or resection of PETs and two remain under observation. Nine of the 13 patients underwent transduodenal exploration to excise gastrinoma(s). One patient had lymph node metastases found at operation. There was no death. Self-limiting pancreatic fistula in five patients and biliary fistula in one., Conclusion: Early and aggressive screening using EUS identifies PETs in asymptomatic patients with MEN-1. Detection of tumours at an early stage, before the development of symptoms, lymph node metastases or liver metastases, may facilitate prompt surgical intervention and improve prognosis., (Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)