Ultrafast intraoperative parathyroid hormone monitoring system: prospective, multicentre, clinical validity study.

BACKGROUND: Intraoperative parathyroid hormone (PTH) monitoring is a proven and reliable adjunct to parathyroid surgery, able to improve the outcomes and efficiency of the diagnostic and therapeutic pathway for patients with primary hyperparathyroidism. This study evaluated the innovative, compact, fully automated NBCL CONNECT Analyzer, which can measure whole-blood PTH in 5 min. METHODS: A prospective multicentre study was conducted in stages: results reviews, recommendations, and implementation of improvements to the mechanical design, components of cartridges, calibration, and sampling protocols. Patients undergoing parathyroidectomy had PTH levels measured on the Analyzer and main laboratory platforms, either Roche or Abbott. The Miami criterion of a 50% drop in PTH concentration was used to define biochemical cure during surgery, and normal postoperative calcium level as cure of primary hyperparathyroidism. Measurements on the Analyzer were done by laboratory staff in London and nurses in Stuttgart. The Pearson coefficient (R) and Wilcoxon test were used for statistical analysis. RESULTS: Some 234 patients (55 male, 179 female) with a median age of 58.5 (age full range 15-88) years underwent parathyroidectomy (195 minimally invasive, 38 bilateral neck exploration, 1 thoracoscopic; 12 conversions) for primary hyperparathyroidism between November 2021 and July 2022. Primary hyperparathyroidism was cured in 225 patients (96.2%). The sensitivity, specificity, and overall accuracy of the Analyzer assay in predicting biochemical cure were 83.9, 100, and 84.8% in phase 1; 91.2, 100, and 91.3% in phase 2; and 98.6, 100, and 98.6% in phase 3. There were no false-positive results (positive predictive value 100%). Correlations between Analyzer measurements and those obtained using the Roche device were very strong (R = 0.98, P < 0.001 in phase 1; R = 0.92, P < 0.001 in phase 2; R = 0.94, P < 0.001 in phase 3), and correlations for Analyzer readings versus those from the Abbott platform were strong (R = 0.82, P < 0.001; R = 0.89, P < 0.001; R = 0.91, P < 0.001). The Analyzer showed continued good mechanical performance, with stable and repeatable operations (calibrations, quality controls). Introducing a stricter sampling protocol and improvements in the clot-detecting system led to a decrease in the number of clotted samples and false-negative results. Outcomes were not affected by measurements performed either by nurses or laboratory staff. CONCLUSION: Intraoperative PTH monitoring during parathyroid surgery can be done accurately, simply, and quickly in whole blood using the Analyzer.

Paediatric differentiated thyroid carcinoma: a UK National Clinical Practice Consensus Guideline.

This guideline is written as a reference document for clinicians presented with the challenge of managing paediatric patients with differentiated thyroid carcinoma up to the age of 19 years. Care of paediatric patients with differentiated thyroid carcinoma differs in key aspects from that of adults, and there have been several recent developments in the care pathways for this condition; this guideline has sought to identify and attend to these areas. It addresses the presentation, clinical assessment, diagnosis, management (both surgical and medical), genetic counselling, follow-up and prognosis of affected patients. The guideline development group formed of a multi-disciplinary panel of sub-speciality experts carried out a systematic primary literature review and Delphi Consensus exercise. The guideline was developed in accordance with The Appraisal of Guidelines Research and Evaluation Instrument II criteria, with input from stakeholders including charities and patient groups. Based on scientific evidence and expert opinion, 58 recommendations have been collected to produce a clear, pragmatic set of management guidelines. It is intended as an evidence base for future optimal management and to improve the quality of clinical care of paediatric patients with differentiated thyroid carcinoma.

Development of [18F]AldoView as the First Highly Selective Aldosterone Synthase PET Tracer for Imaging of Primary Hyperaldosteronism.

The purpose of this study was to synthesize a fluorine-18 labeled, highly selective aldosterone synthase (hCYP11B2) inhibitor, [18F]AldoView, and to assess its potential for the detection of aldosterone-producing adenomas (APAs) with positron emission tomography in patients with primary hyperaldosteronism (PHA). Using dibenzothiophene sulfonium salt chemistry, [18F]AldoView was obtained in high radiochemical yield in one step from [18F]fluoride. In mice, the tracer showed a favorable pharmacokinetic profile, including rapid distribution and clearance. Imaging in the adrenal tissue from patients with PHA revealed diffuse binding patterns in the adrenal cortex, avid binding in some adenomas, and "hot spots" consistent with aldosterone-producing cell clusters. The binding pattern was in good visual agreement with the antibody staining of hCYP11B2 and distinguished areas with normal and excessive hCYP11B2 expression. Taken together, [18F]AldoView is a promising tracer for the detection of APAs in patients with PHA.

Misleading 68 GALLIUM-dotatate PET scan in a patient with a history of a phaeochromocytoma: Unsuspected uptake in papillary thyroid carcinoma metastases.

Scanning for somatostatin receptors using 68 Ga-dotatate positron emission tomography with co-registration with computed tomography or magnetic resonance imaging is now in widespread use for the identification of neuroendocrine tumours, phaeochromocytomas, and paragangliomas and their metastases. We present a case where a patient with a phaeochromocytoma showed uptake in her neck considered diagnostic of a head-and-neck paraganglioma, which was subsequently confirmed to be a metastatic papillary thyroid carcinoma. We alert clinicians to such falsely-identified tumours using this extensively used imaging technique.

Treating papillary and follicular thyroid cancer in children and young people: Single UK-center experience between 2003 and 2018.

AIM: Differentiated thyroid cancer (DTC) in children and adolescents is rare and data about its presentation and management are not well known. The aim of this study was to provide evidence of the current practice in the United Kingdom before the launch of the Rare National Paediatric Endocrine Tumours Guidelines (to be published in 2020). METHODS: Seventy-two children and adolescents with DTC (<18 years) who were treated at our institution between 2003 and 2018 were identified and their presentation, treatment and outcomes were reviewed. RESULTS: Median age at presentation was 12.7 years [range: 1-18] and fifty-two (72%) were girls. Fifty (69.4%) children and adolescents presented with a thyroid nodule. Thirteen (18%) had cervical adenopathy and seven of them (54%) underwent an excision biopsy under GA. Eight patients (11%) had evidence of lung metastases at presentation. Twenty-four patients (33%) underwent a hemithyroidectomy and 22 of those had a completion thyroidectomy subsequently, ten (14%) a total thyroidectomy alone and 37 (51%) a total thyroidectomy with lymph nodes dissection. Seventy patients (97%) underwent adjuvant RAI at our institution. The median number of children and adolescents managed per year was five [range: 0-10]. After an overall median follow-up of 40 months, eight patients (11%) had developed recurrent disease. The 1- and 5-year recurrence-free-survival-rates were 93% and 87%, respectively. Overall survival was 100%, with eight children and adolescents (11%) being alive with disease. CONCLUSION: This study confirms that DTC in children and adolescents is uncommon, is frequently advanced at presentation and has considerable recurrence rates. Despite this, overall survival is excellent. Although the work-up was generally appropriate (image-guided cytology), open biopsy for the diagnosis of lymph node involvement was still employed. The introduction of a specific UK guideline for this age-group will likely result in more tailored-made treatment-pathways and thereby hopefully improve quality and outcomes even further. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level IV.

The value of 18F-FDG PET-CT and 131I-norcholesterol scintigraphy in the characterization of high-risk adrenal masses.

PURPOSE: To assess the value of F-FDG PET-computed tomography (CT) and I-norcholesterol scintigraphy in noninvasive characterization of high-risk adrenal lesions using surgical pathology as the gold standard. METHODS: We retrospectively reviewed clinical cases referred to the adrenal multidisciplinary team in a tertiary centre over the last 6 years. Inclusion criteria were the presence of indeterminate adrenal lesions and performance of combined imaging with 2-deoxy-2-[fluorine-18] fluoro- D-glucose Positron emission tomography/ computed tomography and I-norcholesterol scans. The accuracy of CT, PET-CT and I-norcholesterol findings was assessed by comparison with the postoperative histopathological outcome. RESULTS: Sixteen patients fulfilled the inclusion criteria. Ten underwent unilateral adrenalectomy, and six had clinical follow-up. The number of cases categorized as concerning on the basis of unenhanced CT, F-FDG PET-CT and I-norcholesterol was 11, 9 and 2, respectively. The mean diameter of adrenal lesions was 4.5 ± 1.9 cm. Average SUVmax of the FDG-avid adrenal lesions was 5.0 ± 2.0 (range 3.5-9.7). Fourteen adrenal masses showed I-norcholesterol uptake. All adrenal masses turned out to be benign lesions. CONCLUSION: Conventional CT and FDG PET parameters are not adequately specific for determination of a benign lesion in this selected cohort of high-risk patients. Use of I-norcholesterol in this patient cohort may provide additional value.

Late Recovery of Parathyroid Function after Total Thyroidectomy in Children and Adults: Is There a Difference?

BACKGROUND: Parathyroid failure after total thyroidectomy is the commonest adverse event amongst both children and adults. The phenomenon of late recovery of parathyroid function, especially in young patients with persistent hypoparathyroidism, is not well understood. This study investigated differences in rates of parathyroid recovery in children and adults and factors influencing this. METHODS: A joint dual-centre database of patients who underwent a total thyroidectomy between 1998 and 2018 was searched for patients with persistent hypoparathyroidism, defined as dependence on oral calcium and vitamin D supplementation at 6 months. Demographic, surgical, pathological, and biochemical data were collected and analysed. Parathyroid Glands Remaining in Situ (PGRIS) score was calculated. RESULTS: Out of 960 patients who had total thyroidectomy, 94 (9.8%) had persistent hypoparathyroidism at 6 months, 23 (24.5%) children with a median [range] age 10 [0-17], and 71 (75.5%) adults aged 55 [25-82] years, respectively. Both groups were comparable regarding sex, indication, extent of surgery, and PGRIS score. After a median follow-up of 20 months, the parathyroid recovery rate was identical for children and adults (11 [47.8%] vs. 34 [47.9%]; p = 0.92). Sex, extent, and indication for surgery had no effect on recovery (all p > 0.05). PGRIS score = 4 (HR = 0.48) and serum calcium >2.25 mmol/L (HR = 0.24) at 1 month were associated with a decreased risk of persistent hypoparathyroidism on multivariate analysis (p < 0.05). CONCLUSION: Almost half of patients recovered from persistent hypoparathyroidism after 6 months; therefore, the term persistent instead of permanent hypoparathyroidism should be used. Recovery rates of parathyroid function in children and adults were similar. Regardless of age, predictive factors for recovery were PGRIS score = 4 and a serum calcium >2.25 mmol/L at 1 month.

Children are at a high risk of hypocalcaemia and hypoparathyroidism after total thyroidectomy.

PURPOSE: Disruption of calcium homeostasis is the most common complication after total thyroidectomy in adults. We explored the incidence and risk factors of hypocalcaemia and hypoparathyroidism after total thyroidectomy in children (≤18 years of age). METHODS: One hundred six children underwent total thyroidectomy. Patient, operative and outcome data were collected and analyzed. RESULTS: The indication for surgery was Graves' disease in 52 children (49.1%), Multiple Endocrine Neoplasia type-2 in 36 (33.9%), multinodular goiter in 3 (2.8%) and follicular/papillary thyroid carcinoma in 15 (14.2%). Neck dissection was performed in 23 children (18.9%). In 14 children (13.2%), autotransplantation was performed; in 31 (29.2%), ≥1 glands were found in the specimen. Hypocalcaemia within 24 h of thyroidectomy was observed in 63 children (59.4%) and 52 (49.3%) were discharged on supplements. Hypoparathyroidism at 6 months persisted in 23 children (21.7%). The ratios of all forms of calcium-related-morbidity were larger among children with less than four parathyroid glands remaining in situ: hypocalcaemia within 24 h of thyroidectomy (54.0% versus 47.5%; p = 0.01), hypoparathyroidism on discharge (64.4% versus 37.7%; p = 0.004) and long-term hypoparathyroidism (31.1% versus 14.8%; p = 0.04). CONCLUSION: The incidence of postoperative hypocalcaemia and hypoparathyroidism among children undergoing total thyroidectomy is considerable. The inability to preserve the parathyroid glands in situ during surgery seems an important factor. For optimal outcomes, the parathyroid glands should be preserved in situ. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level IV.

Impact of intraoperative parathyroid hormone monitoring on the management of patients with primary hyperparathyroidism.

BACKGROUND/OBJECTIVE: Intraoperative parathyroid hormone (IOPTH) monitoring during surgery for primary hyperparathyroidism (PHPT) could improve cure rate and simplify current care pathways. This study assesses the performance of US, MIBI and IOPTH monitoring and their impact on outcomes and perioperative strategy. DESIGN: This is a retrospective study of a prospectively maintained database of patients who underwent parathyroidectomy guided by preoperative US, MIBI and IOPTH monitoring. Test performance (sensitivity, specificity, PPV, NPV, accuracy) and IOPTH added value (percentage of patients in whom test contributed to achieving cure) were calculated. RESULTS: A total of 617 patients (median age 59 years, 75% females), 603 (97.7%) of them cured, were included in analysis. Sensitivity of US was higher than MIBI (78.2% vs 70%, P < 0.05), but both were inferior to IOPTH (98.6%, P < 0.05). US and MIBI were more sensitive at detecting single gland disease (SGD) than multigland disease (MGD) (85% vs 55% and 77.5% vs 45.5%, respectively, P < 0.05), while IOPTH performed well in both situations (98.8% vs 96.7%, P > 0.05). In 41 patients with incorrect US predictions, MIBI gave correct result only in 12 (29.3%) cases, while IOPTH gave correct predictions in all but one patient (97.6%). Minimally invasive parathyroidectomy (MIP) was completed in 409 patients, with a similar completion rate regardless whether both or one scan was positive. IOPTH added value was significant in whole cohort (14%) and in subgroups of patients with concordant vs discordant scans, minimally invasive vs conventional surgery, and initial vs reoperative surgery. CONCLUSIONS: Intraoperative parathyroid hormone monitoring is more accurate at predicting cure than US and MIBI are at identifying abnormal glands in patients undergoing parathyroidectomy for PHPT and significantly contributes to cure rate in range of clinical scenarios. This implies that its routine use could facilitate successful surgery in patients with single positive imaging and increase number of MIPs while maintaining high cure rate.

Phaeochromocytomas and paragangliomas: A difference in disease behaviour and clinical outcomes.

BACKGROUND: Phaeochromocytomas and paragangliomas arise from the same chromaffin cell, but evidence suggests they do not represent a single clinical entity. The aim of this study was to compare clinical presentations, outcomes of surgical and oncological treatments and survival in patients with phaeochromocytomas and paragangliomas. METHODS: A retrospective review was undertaken of all patients treated for these conditions at our centre between 1983 and 2012. RESULTS: One hundred and six patients (88 adults, 18 children) with phaeochromocytoma (n = 83) or paraganglioma (n = 23) were studied. Catecholamine symptoms and incidentalomas were the main presentations in phaeochromocytoma patients (67% and 17%) respectively, but in those with paragangliomas pain (39%) was more common (P < 0.001). More paragangliomas were malignant (14/23 vs 9/83, P < 0.0001), larger (9.17 ± 4.95 cm vs. 5.8 ± 3.44 cm, P = 0.001) and had a higher rate of conversion to open surgery (P = <0.01), more R2 resections, more postoperative complications and a longer hospital stay (P = 0.014). MIBG uptake in malignant paragangliomas was lower than in malignant phaeochromocytomas (36% vs. 100%, P = 0.002) and disease stabilisation was achieved in 29% and 86% of patients respectively. (90) Y-DOTA-octreotate had a 78% response rate in malignant paragangliomas. CONCLUSION: The clinical differences between paragangliomas and phaeochromocytomas support the view that they should be considered as separate clinical entities.

Aetiology, Diagnosis and Surgical Treatment of Primary Hyperparathyroidism in Children: New Trends.

Primary hyperparathyroidism (PHPT) in children is a rare disorder with sharp contrasts in its presentation and aetiology compared with the disease process in adults. This review outlines the current literature, which is limited to about 200 cases, with reference to the aetiology, clinical features, outcomes of investigations, and surgery in children affected by PHPT. Familial conditions account for almost half of all cases of PHPT in children, suggesting that routine genetic testing would be appropriate. Neonatal severe hyperparathyroidism requires urgent medical attention, and performing total parathyroidectomies offers cure, though conservative management is successful in selected cases. Familial hyperparathyroidism in older children can be caused by conditions such as multiple endocrine neoplasia types 1 and 2a, hyperparathyroidism-jaw tumour syndrome and familial hyperparathyroidism. The role of surgery for this group is discussed. The use of ultrasound and MIBI (99mTc-methoxyisobutylnitrile) scanning appears to accurately localise solitary adenomas in sporadic PHPT, thereby supporting the role of minimally invasive parathyroidectomy in children. © 2015 S. Karger AG, Basel.

Thyroid Surgery in Children: Clinical Outcomes.

AIM: The aim of this study was to review the outcomes of thyroid surgery in children operated for both benign and malignant conditions. PATIENTS AND METHOD: Demography, clinical features, and surgical outcomes were noted retrospectively for operations performed during the last 23 years. Results were analyzed using Fisher exact test and Woolf (logit) method with p value < 0.05 considered as significant. RESULTS: In total, 61 children (43 girls and 18 boys) underwent thyroidectomy for benign (70%) and malignant (30%) conditions. Median follow-up period was 1.4 years. In the benign group, 84% children had Graves disease and 16% had other conditions. In this study, 42% children had total, 22% had near-total, 27% had subtotal, and 9% had type 2 hemithyroidectomy. In the malignant group, 50% had multiple endocrine neoplasia, 33% had papillary, 11% had follicular cancer, and 6% had B-cell lymphoma. Fifty percent children had prophylactic thyroidectomy, 44% had total thyroidectomy plus lymphadenectomy, and 6% had hemithyroidectomy. At the time of surgery, children with benign conditions were older than those with malignancy (median, 12 vs. 7.5 years). There were no incidents of postoperative bleeding or infection. Hypocalcemia was significantly more frequent in the malignant group (39 vs. 9%, p value = 0.01). The type of recurrent laryngeal nerve (RLN) injury was more serious in the benign group (one bilateral and one unilateral permanent injury) than in the malignant group (transient hoarseness in three). Overall rate of complications was higher for operations for malignancy (56 vs. 28%, p value = 0.07). In Graves disease, the subtotal thyroidectomies had a recurrence of 30% but no recurrence was seen following total or near-total thyroidectomy group (p value = 0.01). There was no recurrence in the malignant group. Children operated after 2000 were younger than those operated before 2000 (median age, 9 vs. 14 years). Malignant conditions were more common in children operated after 2000 in comparison to before 2000 (55 vs. 10%). CONCLUSION: Benign conditions are commonest indications for thyroid surgery in children but the incidence of surgery for malignant conditions is rising. Overall rate of complications, especially hypocalcemia, is higher after surgery for malignancy but all cases of permanent RLN injury were in benign group. Total or near total thyroidectomy prevents recurrence of thyrotoxicosis and is an operation of choice for Graves disease.

Value of sonographic features in predicting malignancy in thyroid nodules diagnosed as follicular neoplasm on cytology.

BACKGROUND: The cytological diagnosis of follicular neoplasm (Thy3F) remains a diagnostic challenge. The main aim of this study was to stratify the risk of malignancy in thyroid nodules diagnosed as Thy3F on cytology (Thy3F) using thyroid imaging reporting and data system (TIRADS). METHODS: A database of thyroid nodules with Thy3F cytological results from ultrasound-guided FNA (US-FNA) between January 2007 and March 2014 was studied retrospectively. Information on patient demographics, ultrasound characteristics and final histology of the nodules was collated. The number of suspicious US features of each thyroid nodule was counted based on TIRADS. The malignancy rate of each of the TIRADS category was also calculated based on the final histological outcomes of the nodules and compared to that calculated using a recently proposed thyroid malignancy risk prediction model. RESULTS: The overall malignancy rate of Thy3F cytology was 24·3%. There were significantly higher percentages of malignant nodules with irregular margins (20·0% vs 0%, P = 0·000), hypo-echogenicity (74·3% vs 51·4%, P = 0·013) and taller-than-wide morphology (17·1% vs 0·9%, P = 0·001) when compared to benign nodules. The risk of malignancy increased with advancing TIRADS score: TIRADS 4A (14·3%), TIRADS 4B (23·1%), TIRADS 4C (87·5%) and TIRADS 5 (100%). The malignancy rate calculated using the prediction model similarly increased with advancing TIRADS score: TIRADS 4A (6·2%), TIRADS 4B (32·5%), TIRADS 4C (79·9%) and TIRADS 5 (90%). CONCLUSION: Thyroid nodules with TIRADS scores 4C and 5 should be considered for single definitive surgery in view of the high malignant rate.

Adrenal cancer in neurofibromatosis type 1: case report and DNA analysis.

UNLABELLED: Adrenal cortical carcinoma (ACC) has previously only been reported in eight patients with type 1 neurofibromatosis (NF1). There has not been any clear evidence of a causal association between NF1 gene mutations and adrenocortical malignancy development. We report the case of a 49-year-old female, with no family history of endocrinopathy, who was diagnosed with ACC on the background of NF1, due to a novel germline frame shift mutation (c.5452_5453delAT) in exon 37 of the NF1 gene. A left adrenal mass was detected by ultrasound and characterised by contrast computerised tomography (CT) scan. Biochemical tests showed mild hypercortisolism and androgen excess. A 24-h urinary steroid profile and (18)flouro deoxy glucose PET suggested ACC. An open adrenalectomy was performed and histology confirmed ACC. This is the first reported case with DNA analysis, which demonstrated the loss of heterozygosity (LOH) at the NF1 locus in the adrenal cancer, supporting the hypothesis of an involvement of the NF1 gene in the pathogenesis of ACC. LOH analysis of the tumour suggests that the loss of neurofibromin in the adrenal cells may lead to tumour formation. LEARNING POINTS: ACC is rare but should be considered in a patient with NF1 and adrenal mass when plasma metanephrines are normal.Urinary steroid metabolites and PET/CT are helpful in supporting evidence for ACC.The LOH at the NF1 region of the adrenal tumour supports the role of loss of neurofibromin in the development of ACC.

Intrathyroidal ectopic thymic tissue mimicking thyroid cancer in children.

OBJECTIVE: To increase awareness of the important differential diagnosis between thyroid cancer and intrathyroidal ectopic thymic tissue when performing neck ultrasound (US) in pediatric patients. METHODS: We report 2 cases of intrathyrodal thymic tissue that were initially referred as possible papillary thyroid cancer (PTC). US and cytologic features of these lesions are described, and the distinguishing US characteristics of intrathyroidal thymic tissue versus PTC are discussed. RESULTS: Two pediatric patients who underwent thyroid US were diagnosed with thyroid nodules suggestive of PTC. The suspected lesions in both patients exhibited an echo texture identical to the normal thymus gland. Fine-needle aspirate (FNA) biopsy of the nodule in the first case revealed numerous lymphocytes with positive immunocytochemical staining for CD3, confirming a T cell phenotype. The second patient underwent follow-up US imaging 8 months later that showed stability of the intrathyroidal nodule. CONCLUSION: Intrathyroidal ectopic thymic tissue can be mistaken for PTC as both conditions have similar US features. Increased awareness of this unique mimicry may help to avoid unnecessary invasive investigations and surgery in these young patients.

Glucagon-like peptide-1 versus somatostatin receptor targeting reveals 2 distinct forms of malignant insulinomas.

UNLABELLED: Glucagon-like peptide-1 (GLP-1) receptor imaging is superior to somatostatin receptor subtype 2 (sst(2)) imaging in localizing benign insulinomas. Here, the role of GLP-1 and sst(2) receptor imaging in the management of malignant insulinoma patients was investigated. METHODS: Eleven patients with malignant insulinoma were prospectively included. (111)In-[Lys(40)(Ahx-diethylenetriaminepentaacetic acid [DTPA])NH(2)]-exendin-4 SPECT/CT, (68)Ga- DOTATATE PET/CT, and in vitro receptor autoradiography were performed to assess the receptor status and to evaluate the detection rate. RESULTS: GLP-1 receptor targeting was positive in 4 of 11 patients, and sst(2) receptor expression was positive in 8 of 11. In only 1 patient were both receptors expressed. In 1 patient, GLP-1 receptor imaging was the only method that successfully localized the primary tumor in the pancreas. In 3 patients with sst(2)-expressing tumors, DOTATATE radiotherapy was effectively applied. CONCLUSION: As opposed to benign insulinomas, malignant insulinomas often lack GLP-1 receptors. Conversely, malignant insulinomas often express sst(2), which can be targeted therapeutically.

Clinical presentation and waiting time targets do not affect prognosis in patients with pancreatic cancer.

INTRODUCTION: The prognosis of patients with pancreatic cancer remains poor despite recent advances in treatment. It is not known whether delays in referring, diagnosing and treating these patients and the way they present can affect their survival. AIMS: In our study we investigated the impact of clinical presentation (jaundice, abdominal pain, weight loss) and delays in management of these patients on their treatment and survival. METHODS: Data on all patients with pancreatic cancer referred to the Pancreatic Unit (1997-2002) were collected prospectively and analysed using SPSS 16((R).) The delay in diagnosis and treatment for each patient was measured by estimating the time from the beginning of symptoms to the date of the referral letter (T1), the time from the referral date to the date of first review at the Unit (T2) and the time from date of review to the date of diagnosis/treatment (T3). Treatments were defined as 1) pancreatic resections, 2) gastric and biliary bypass and 3) biliary stents. The term 'operability' was used to describe patients thought to have a potentially removable tumour and had an operation and 'resectability' applied to the patients whose tumour was actually removed at the operation. Follow-up time and survival were recorded by reviewing the patient's notes, hospital electronic databases and by contacting patients General Practitioners. RESULTS: There were a total of 355 patients with pancreatic cancer. Median age at diagnosis was 64 (i.q.r. 56-71) years and median follow-up was 8 (i.q.r. 4-14) months. The overall 1, 3 and 5 years patient's survival was 26%, 5% and 4% respectively. 1, 3 and 5 years survival of inoperable patients was 24%, 2% and 0% and for operable patients was 35%, 13% and 9% respectively. The median survival time for those patients that underwent operation was significantly higher than those that did not (12 vs 6 months, p < 0.001). The overall median time from initial symptoms to diagnosis/treatment (T1 + T2 + T3) was 102 (i.q.r. 56-182) days, T1 was 65 (i.q.r. 31-143), T2 17 (i.q.r. 8-28) and T3 11 (i.q.r. 6-21) days. The time delay from symptoms to referral (T1) had minimal clinical relevance to survival, with a hazard ratio of only 1.001 (95% CI 0.001-0.002, p = 0.043) per day. Of all 355 patients, 305 (86%) were reviewed and treated within 62 days from the GP referral (T2 + T3). There was no significant difference in operability, resectability and survival of patients that were diagnosed/treated before or after 62 days from referral (T2 + T3) (median months 6.5 and 7.9 respectively, p = 0.134). Patients presenting with jaundice were referred (T1, median 56 vs 103) and diagnosed/treated (T2 + T3, median 96 vs 130) days (p < 0.001) sooner, had a higher operability rate (33% vs 21%, p = 0.035) but not a significantly higher resectability rate of (37% vs 29%) (p = 0.608). Isolated or combined mode of clinical presentation had no significant effect on survival (p = 0.965). On multivariate regression analysis, prognostic factors of survival were a resectable tumour and the time from the beginning of symptoms to referral. CONCLUSION: This study showed that pre-hospital delays in referring patients to a specialist unit, but not hospital related 62 days target, had an no impact on operability, resectability and survival. Clinical presentation also had no impact on the survival. We confirmed that pancreatic resection is the most important factor in determining the length of survival in patients with pancreatic cancer. Our study implies that the successful implementation of the 62 days National Cancer Waits Target across the UK is unlikely to have an impact on prognosis in patients with pancreatic cancer. Focusing on early referral to specialist Pancreatic Units might be more effective.

Complications and diagnostic difficulties arising from biliary self-expanding metal stent insertion before definitive histological diagnosis.

BACKGROUND: Self-expanding metal bile duct stents provide good palliation for inoperable malignant disease. However, problems may arise if metal stents are inserted before definitive histological diagnosis. The aim of this study was to evaluate the outcome of such patients. METHODS: A retrospective case note review was conducted of patients referred to a tertiary pancreaticobiliary center between 1992 and 2004 in whom a metal bile duct stent was inserted for presumed unresectable malignant disease before definitive histological diagnosis. RESULTS: There were 21 patients identified. Final diagnoses were: group 1, benign disease (n = 3); group 2, resectable malignancy (n = 2); group 3, unresectable malignancy (n = 12); and group 4, diagnosis remains uncertain (n = 4). During a follow-up of 22, 38 and 111 months, the patients in group 1 had one, eight and five episodes of stent occlusion. In group 2, both patients underwent pancreaticoduodenectomy for ampullary carcinoma, 2 and 6 months after presentation. In group 3, the median time to a confirmed malignant diagnosis was 2 months (range 1-27 months). In group 4, a median of two biopsies (range 1-4) were negative for malignancy, during a median follow up of 13 months (range 3-46). Overall in eight patients, the metal stents caused artifacts on computed tomography and/or were associated with tissue in-growth making the differentiation between benign and malignant disease difficult. CONCLUSION: These cases indicate that metal bile duct stent insertion before definitive histological diagnosis can be problematic. A proportion of cases will have benign strictures and in others the confirmation of malignancy may be made more difficult.