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Multiple Endocrine Neoplasia type 1 (MEN1) Clinical Practice Guidelines (2012) are predominantly based on expert opinion due to limited available evidence at the time, leaving room for interpretation and variation in practices. Evidence on the natural course of MEN1-related neuroendocrine tumours (NET) and the value of screening programs has increased and new imaging techniques have emerged. The aim of this study is to provide insight in the current practices of screening and surveillance for MEN1-related NETs in ENETS Centers of Excellence (CoEs). A clinical practice questionnaire was distributed among all 65 ENETS CoEs. Response rate was 91% (59/65). In 14% of CoEs <10 patients, in 50% 10-49, in 31% 50-100 and in 3 centres (5%) >100 patients with MEN1 are seen. Practices with regard to screening and surveillance of NETs were markedly heterogeneous. Differences between countries were noted in the use of gut hormones for biochemical screening and the choice for imaging modality for screening/surveillance of pancreatic NETs (PanNETs). Magnetic resonance imaging (MRI) is the preferred modality for screening and surveillance of PanNETs, whereas this is computed tomography (CT) for thoracic NETs. Practices regarding screening for thoracic NETs were more homogeneous among larger volume CoEs, with longer screening intervals. The majority of CoEs tailored the surveillance of small pancreatic and lung NETs to observed growth rate. 68% of CoEs advise patients with clinical MEN1 with negative genetic testing to undergo periodic screening like mutation-positive patients. In conclusion, there is still marked heterogeneity in practice, although there are also common trends. Differences were sometimes associated with volume or country, but often no association was found. This underscores the need for clear and evidence-based practice recommendations., (© 2024 The Author(s). Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

The incidence of differentiated thyroid cancer (DTC) has been increasing worldwide, mostly, as an increase in the incidental detection of micro papillary thyroid carcinomas (microPTCs), many of which are potentially overtreated, as suggested by the unchanged mortality. Several international guidelines have suggested a less aggressive approach. More recently, it has been shown that active surveillance or minimally invasive treatments (MIT) are good alternatives for the management of these patients. In this context, patient participation in the decision-making process is paramount. The Endocrine Task Force of the European Organisation for Research and Treatment of Cancer (EORTC) has undertaken the task to establish consensus and define its position based on the scientific evidence concerning, 1) the current state of diagnostic and management options in microPTCs, including the current opinion of physicians about shared decision making (SDM), 2) the available evidence concerning patients' needs and the available decision instruments, and 3) to provide practical suggestions for implementation of SDM in this context. To improve SDM and patients' participation, knowledge gaps and research directions were highlighted., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown., Design: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS)., Results: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%)., Conclusions: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

1: ESGE recommends endoscopic ultrasonography (EUS) as the best tool to characterize subepithelial lesion (SEL) features (size, location, originating layer, echogenicity, shape), but EUS alone is not able to distinguish among all types of SEL.Strong recommendation, moderate quality evidence. 2: ESGE suggests providing tissue diagnosis for all SELs with features suggestive of gastrointestinal stromal tumor (GIST) if they are of size > 20 mm, or have high risk stigmata, or require surgical resection or oncological treatment.Weak recommendation, very low quality evidence. 3: ESGE recommends EUS-guided fine-needle biopsy (EUS-FNB) or mucosal incision-assisted biopsy (MIAB) equally for tissue diagnosis of SELs ≥ 20 mm in size.Strong recommendation, moderate quality evidence. 4: ESGE recommends against surveillance of asymptomatic gastrointestinal (GI) tract leiomyomas, lipomas, heterotopic pancreas, granular cell tumors, schwannomas, and glomus tumors, if the diagnosis is clear.Strong recommendation, moderate quality evidence. 5: ESGE suggests surveillance of asymptomatic esophageal and gastric SELs without definite diagnosis, with esophagogastroduodenoscopy (EGD) at 3-6 months, and then at 2-3-year intervals for lesions < 10 mm in size, and at 1-2-year intervals for lesions 10-20 mm in size. For asymptomatic SELs > 20 mm in size that are not resected, ESGE suggests surveillance with EGD plus EUS at 6 months and then at 6-12-month intervals.Weak recommendation, very low quality evidence. 6: ESGE recommends endoscopic resection for type 1 gastric neuroendocrine neoplasms (g-NENs) if they grow larger than 10 mm. The choice of resection technique should depend on size, depth of invasion, and location in the stomach.Strong recommendation, low quality evidence. 7: ESGE suggests considering removal of histologically proven gastric GISTs smaller than 20 mm as an alternative to surveillance. The decision to resect should be discussed in a multidisciplinary meeting. The choice of technique should depend on size, location, and local expertise.Weak recommendation, very low quality evidence. 8: ESGE suggests that, to avoid unnecessary follow-up, endoscopic resection is an option for gastric SELs smaller than 20 mm and of unknown histology after failure of attempts to obtain diagnosis.Weak recommendation, very low quality evidence. 9: ESGE recommends basing the surveillance strategy on the type and completeness of resection. After curative resection of benign SELs no follow-up is advised, except for type 1 gastric NEN for which surveillance at 1-2 years is advised.Strong recommendation, low quality evidence. 10: For lower or upper GI NEN with a positive or indeterminate margin at resection, ESGE recommends repeating endoscopy at 3-6 months and another attempt at endoscopic resection in the case of residual disease.Strong recommendation, low quality evidence., Competing Interests: J.Y. Blay’s department has received research support from Novartis, Bayer, Deciphera, and Roche (all from 2018–2021). P.H. Deprez has received lecture fees from Olympus (2010–2021) and Erbe (2010–2020). R. Gincul has received honoraria for lectures and speaker’s fees from Olympus (2013–2014, 2018–2019) and from Boston Scientific (2016), and for training workshops from IPSEN (2015–2021). J.E. van Hooft’s department has received research grants from Cook Medical (2014–2019) and Abbott (2014–2017); she has received lecture fees from Medtronics (2014–2015, 2019), Cook Medical (2019), and Abbvie (2021), and consultancy fees from Boston Scientific (2014–2017) and Olympus (2021). L.M.G. Moons has provided consultancy on new products to Boston Scientific (1 Jan 2021–31 Dec 2021). M. Polkowski had a speaker and consultancy agreement with Olympus (2018–2021) and a consultancy agreement with Boston Scientific (2018–2019); he is a Co-Editor of Endoscopy. I. Borbath, G. Fernandez Esparrach, T.G. Moreels, E. Nieveen van Dijkum, P.P. Nunes, D. O’Toole, A. Seicean, and M. Vieth have no competing interests., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

Background: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors., Methods: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1-2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel's C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence., Results: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78-88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70-0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80)., Conclusions: External validity of this prediction model for recurrence after curative surgery for grade 1-2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background: Surgery for small bowel neuroendocrine neoplasms (SB-NEN) might result in vascular compromise of the remaining bowel due to resection of lymph node metastases in close proximity to main mesenteric vessels. Fluorescence angiography (FA) has been described as a safe technique to assess perfusion during gastro-intestinal surgery. This study aimed to evaluate the potential value of intraoperative FA during surgery for SB-NEN., Methods: This study included patients undergoing surgery for SB-NEN of any stage. The planned level of transection was marked by the surgeon, after which FA using indocyanine green (ICG) was performed. The primary study outcome was change in management due to FA., Results: Ten consecutive patients with SB-NEN were included, all with metastatic lymph nodes close to main mesenteric vessels. FA use led to management changes in eight patients (80%); four patients had less bowel resected with a preserved length of 5-35 cm. The other four patients had more extended bowel resections with an additional length varying from 3 to 25 cm. The median postoperative stay was 4 days (interquartile range 4-6). No anastomotic leakage occurred., Conclusion: This is the first known series describing preliminary results of FA during SB-NEN surgery. FA led to a management change in 80% of patients with better tailoring the extent of resection of small bowel. Structural implementation of FA to assess small bowel perfusion after dissection for small bowel NET results in change of management, either by preserving small bowel or resecting ill-perfused small bowel., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: PTEN hamartoma tumor syndrome (PHTS) represents a group of syndromes caused by a mutation in the PTEN gene. Children with a germline PTEN mutation have an increased risk of developing differentiated thyroid carcinoma (DTC). Several guidelines have focused on thyroid surveillance in these children, but studies substantiating these recommendations are lacking., Objective: The present study intends to provide the available evidence for a thyroid carcinoma surveillance program in children with PHTS., Methods: An extensive literature search was performed to identify all studies on DTC in pediatric PHTS patients. Two pediatric cases are presented to illustrate the pros and cons of thyroid carcinoma surveillance. Recommendations for other patient groups at risk for DTC were evaluated. Consensus within the study team on recommendations for children with PHTS was reached by balancing the incidence and behavior of DTC with the pros and cons of thyroid surveillance, and the different surveillance methods., Results: In 5 cohort studies the incidence of DTC in childhood ranged from 4 to 12%. In total 57 cases of DTC and/or benign nodular disease in pediatric PHTS patients were identified, of which 27 had proven DTC, with a median age of 12 years (range 4-17). Follicular thyroid carcinoma (FTC) was diagnosed in 52% of the pediatric DTC patients. No evidence was found for a different clinical behavior of DTC in PHTS patients compared to sporadic DTC., Conclusions: Children with PHTS are at increased risk for developing DTC, with 4 years being the youngest age reported at presentation and FTC being overrepresented. DTC in pediatric PHTS patients does not seem to be more aggressive than sporadic DTC., Recommendations: Surveillance for DTC in pediatric PHTS patients seems justified, as early diagnosis may decrease morbidity. Consensus within the study team was reached to recommend surveillance from the age of 10 years onwards, since at that age the incidence of DTC seems to reach 5%. Surveillance for DTC should consist of yearly neck palpation and triennial thyroid ultrasound. Surveillance in children with PHTS should be performed in a center of excellence for pediatric thyroid disease or PHTS., Competing Interests: The authors have nothing to disclose., (Copyright © 2020 by S. Karger AG, Basel.)

Objective: To perform a nationwide population based study in ATC on incidence, treatment and survival., Design: Retrospective cohort study., Methods: All patients with primary ATC between 1989 and 2016 were identified in the Netherlands Cancer Registry (NCR). Of all these patients excerpts from the pathology reports from PALGA: Dutch Pathology registry were linked to the data of the NCR. Standardized incidences were calculated, survival was estimated using Kaplan-Meier method and univariable statistically significant factors were included in a multivariable regression model., Results: In total, 812 patients were included. Mean standardized incidence rates were 0.18/100 000 (range 0.11-0.27/100 000) with a significant trend over the years with an estimated annual percentage change of 1.3% per year (95% CI 0.4-2.1%). Median overall survival was 2.2 months, and estimated 1-year survival was 12%. Patients without distant metastases at diagnosis had an estimated 1-year survival of 21.6%. Prognostic factors for prolonged survival were double or triple therapy, age below 65 years, M0-status and absence of bilateral lymph node metastases., Conclusions: ATC is rare, but often lethal, form of thyroid cancer, with a median survival of 2 months and 1-year survival of approximately 10%. The incidence is slightly rising in the Netherlands over the past 3 decades. There appears to be a subgroup of patients that survive longer, mainly those with relatively limited disease who underwent double or triple therapy. Further research is needed to define these patients more distinctively.

Pancreatic parenchyma sparing surgery for insulinomas avoids the risk of endocrine and exocrine insufficiency, and potential high-risk anastomoses associated with pancreatic resection. Robotic surgery may be used as an alternative for open pancreatic enucleation without compromising dexterity and 3D-vision. We present the case of a 42-year old woman who presented with sweating, tremor and episodes of hypoglycemia. A fasting test confirmed endogenic insulin overproduction. After inconclusive CT- and MRI imaging, endoscopic ultrasonography showed a hypoechoic lesion, which was fully within the pancreatic head. Although consent was obtained for pancreatoduodenectomy, robotic enucleation seemed feasible. After mobilization, intraoperative ultrasonography was used to identify the lesion and its relation with the pancreatic duct. Dissection was performed using a traction suture, hot shears and bipolar diathermia. A sealant patch was applied for hemostasis and a drain placed. The patient developed a grade B pancreatic fistula for which endoscopic sphincterotomy was performed; the surgical drain could be removed in the outpatient clinic after 20 days. Prospective studies should confirm the short- and long-term benefits of robotic enucleation of insulinomas.

Radiation exposure to the thyroid gland during treatment of childhood, adolescent and young adult cancer (CAYAC) may cause differentiated thyroid cancer (DTC). Surveillance recommendations for DTC vary considerably, causing uncertainty about optimum screening practices. The International Late Effects of Childhood Cancer Guideline Harmonization Group, in collaboration with the PanCareSurFup Consortium, developed consensus recommendations for thyroid cancer surveillance in CAYAC survivors. These recommendations were developed by an international multidisciplinary panel that included 33 experts in relevant medical specialties who used a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. Of the two available surveillance strategies, thyroid ultrasound and neck palpation, neither was shown to be superior. Consequently, a decision aid was formulated to guide the health care provider in counseling the survivor. The recommendations highlight the need for shared decision making regarding whether to undergo surveillance for DTC and in the choice of surveillance modality., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The use of intraoperative neuromonitoring (IONM) in thyroid surgery has steadily increased in recent years. This technique helps to identify different nerves in and around the operation site, such as the recurrent laryngeal nerve (RLN) and the external branch of the superior laryngeal nerve. Particularly in patients who undergo a second operation or a complex procedure for malignancy, the technique's value has been demonstrated. However, in non-complex thyroid operations the risk of vocal cord paresis due to iatrogenic injury of the RLN is 0.1%. Therefore, high quality research with sufficient power to assess the effect of IONM on prevention of vocal cord paresis is scarce, and the routine use of IONM in thyroid surgery is currently not indicated.

Background: Medullary thyroid cancer (MTC) comprises only 4% of all thyroid cancers and originates from the parafollicular C-cells. HIF-1α expression has been implied as an indicator of worse prognosis in various solid tumors. However, whether expression of HIF-1α is a prognosticator in MTC remained unclear. Our aim was to evaluate the prognostic value of HIF-1α in patients with MTC., Methods: All patients with MTC who were operated on between 1988 and 2014 in five tertiary referral centers in The Netherlands were included. A tissue microarray was constructed in which 111 primary tumors could be analyzed for expression of HIF-1α, CAIX, Glut-1, VEGF and CD31 and correlated with clinicopathologic variables and survival., Results: The mean age of patients was 46.3 years (SD 15.6), 59 (53.2%) were male. Of the 111 primary tumors, 49 (44.1%) were HIF-1α negative and 62 (55.9%) were HIF-1α positive. Positive HIF-1α expression was an independent negative indicator for progression free survival (PFS) in multivariate cox regression analysis (HR 3.1; 95% CI 1.3 - 7.3). Five-years survival decreased from 94.0% to 65.9% for the HIF-1α positive group (p=0.007). Even within the group of patients with TNM-stage IV disease, HIF-1α positivity was associated with a worse prognosis, shown by a decrease in 5-years survival of 88.0% to 49.3% (p=0.020)., Conclusion: Expression of HIF-1α is strongly correlated with adverse prognosis of MTC. This could open up new ways for targeted systemic therapy of MTC.

Aim: To determine whether somatostatin receptor scintigraphy (SRS) influences the preoperative staging and clinical management of non-functioning pancreatic neuroendocrine tumours (NF-pNETs)., Materials and Methods: All SRS examinations performed between 2002-2013 were selected. Patients with NF-pNET were included if both computed tomography (CT) and SRS was performed during preoperative staging. The diagnostic accuracy of CT and SRS for detecting NF-pNET metastases was analysed. Altered TNM classification and changed clinical management were calculated. Changed management was defined as a change from surgical resection into systemic treatment or vice versa. NF-pNETs were defined as tumours without clinical symptoms of hormonal hypersecretion., Results: Overall, 62 patients with NF-pNET were included with a mean age of 57 years (SD: 12.4)(2). In 28 patients (45%), CT and SRS were correct and in agreement in the detection of primary tumour/metastases. In 34 patients (55%), one of the techniques was incorrect and therefore, there was no agreement. SRS altered the TNM classification in 14 patients (23%) and clinical management in nine patients (15%). In patients without metastases on CT, SRS detected lymph node metastases in one patient. The sensitivity to detect the primary tumour with CT was 95% and with SRS was 73%. In detecting metastases, the sensitivity and specificity were both 85% for CT versus 80% and 90% for SRS., Conclusion: Overall, CT and SRS were in agreement in the detection of NF-pNET. In NF-pNET without suspicious metastatic lesions on CT, SRS has limited value. SRS may be indicated to confirm lesions suspicious for neuroendocrine tumours metastases., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Treatment of differentiated thyroid carcinoma (DTC) often involves administration of radioactive iodine (I-131) for remnant ablation or adjuvant therapy. As DTC has favorable outcome and the incidence is increasing, concerns have been raised about the possible adverse effects of I-131 therapy. We systematically reviewed the literature to examine the risk of intermediate and long-term adverse effects of I-131 therapy in DTC patients., Methods: Multiple electronic databases were searched up to November 2014 for English-language, controlled studies that reported on the risk of salivary gland dysfunction, lacrimal gland dysfunction, gonadal dysfunction, female reproductive outcomes or second primary malignancies (SPM) after I-131 exposure. The certainty of the evidence found was assessed using GRADE., Results: In total, 37 articles met all inclusion criteria, no studies reporting on adverse effects after I-131 treatment focused solely on children. After exposure to I-131 for DTC, patients experienced significantly more frequently salivary gland dysfunction (prevalence range: 16-54%, moderate-level evidence), lacrimal gland dysfunction (prevalence: 11%, low-level evidence), transient male gonadal dysfunction (prevalence: 35-100%, high-level evidence), transient female gonadal dysfunction (prevalence: 28%, low-level evidence) and SPM (prevalence: 2.7-8.7%, moderate-level evidence) compared to unexposed patients. I-131 therapy seems to have no deleterious effects on female reproductive outcomes (very-low level evidence). The prevalence and severity of adverse effects were correlated to increasing cumulative I-131 activity., Conclusion: Treatment with I-131 for DTC may have significant adverse effects, which seem to be dose dependent. These adverse effects of treatment must be balanced when choosing for I-131 therapy in patients with DTC., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives. The aim of this study was to investigate the detection rate of adrenal incidentalomas and subsequent workup. Design. Retrospective cohort study. Methods. Two investigators evaluated the adrenals on abdominal CT scans. Abnormalities were compared to the original radiology reports and an experienced abdominal radiologist reviewed the CT scans. All additional imaging and laboratory tests were assessed. Results. The investigators detected 44/356 adrenal incidentalomas (12%). In 25 patients an adrenal incidentaloma had been noted in the radiology report. The expert radiologist agreed on 19 incidentalomas in 17 patients, two with bilateral incidentalomas. Of the 25 incidentaloma patients, 4 (16%) patients were screened for hormonal overproduction and 2 (8%) patients had follow-up imaging studies. Conclusions. 12% of the patients had an adrenal incidentaloma (42 of 356). 17 (40%) had initially not been reported by the radiologist. When diagnosed with an adrenal incidentaloma, only a small percentage of patients (16%) is screened or undergoes repeated imaging (8%) as proposed in the National Institutes of Health (NIH) guidelines on adrenal incidentalomas.

Background: Subtotal thyroidectomy is a surgical procedure, in which the surgeon leaves a small thyroid remnant in situ to preserve thyroid function, thereby preventing lifelong thyroid hormone supplementation therapy., Aim: To evaluate thyroid function after subtotal thyroidectomy for Graves' hyperthyroidism., Subjects and Methods: We retrospectively reviewed the medical records of all patients (n = 62) who underwent subtotal thyroidectomy for recurrent Graves' hyperthyroidism between 1992 and 2008 in our hospital. Thyroid function was defined according to plasma TSH and free T4 values., Results: Median followup after operation was 54.6 months (range 2.1-204.2 months). Only 6% of patients were euthyroid after surgery. The majority of patients (84%) became hypothyroid, whereas 10% of patients had persistent or recurrent hyperthyroidism. Permanent recurrent laryngeal nerve palsy and permanent hypocalcaemia were noted in 1.6% and 3.2% of patients, respectively., Conclusion: In our series, subtotal thyroidectomy for Graves' hyperthyroidism was associated with a high risk of postoperative hypothyroidism and a smaller, but significant, risk of persistent hyperthyroidism. Our data suggest that subtotal thyroidectomy seems to provide very little advantage over total thyroidectomy in terms of postoperative thyroid function.

Introduction: Most leg ulcers are vascular based. Only if vascular therapy fails other causes are considered. We report the case of a female with incapacitating leg ulcers caused by a rare condition which was only diagnosed after failing treatment., Presentation of Case: The female had an extensive previous history including diabetes, renal insufficiency and cardiovascular disease and presented with three large and painful ulcers on her left lower leg. Standard treatment with antibiotics, wound excision and additional treatment with hyperbaric oxygen were ineffective. One month post hospital-admission calciphylaxis cutis caused by renal failure induced secondary hyperparathyroidism was diagnosed. Surgical treatment by a parathyroidectomy induced rapid regeneration of the ulcers., Discussion: Our patient's vast comorbidity and previous history had expanded differential considerations causing a delay in diagnosis. Our patient's previous history led us to believe her ulcers were vascular based, however her chronic renal failure appeared responsible for her condition., Conclusion: Although less probable than venous insufficiency and concomittant leg ulcers or other differential considerations, calciphylaxis cutis should be part of the differential diagnosis in any end stage renal disease-patient with unexplained ulcers as an effective therapy is readily available.

A 53-year-old woman presented with fever accompanied by chills and an extremely painful swelling of her right thyroid lobe. She was initially diagnosed as having subacute thyroiditis, but after 14 days her disease appeared to be caused by a destructive suppurative thyroiditis due to Salmonella group C. A pre-existing hyperplastic nodule in the right thyroid lobe was the predisposing factor. Antibiotics were given for several weeks and surgical drainage was performed. Finally a hemithyroidectomy was done to eliminate the predisposing factor.

Objective: To investigate the role of diagnostic laparoscopy and laparoscopic ultrasonography in the staging of carcinoma of the gastric cardia that is involving the distal oesophagus., Design: Retrospective consecutive case series., Setting: Tertiary care centre, The Netherlands., Subjects: 48 patients (34 men and 14 women, median age 63 years, range 39-84) who presented with tumours of the gastric cardia that involved the distal oesophagus and in whom non-invasive staging had not shown unresectable locoregional disease or distant metastases., Interventions: In addition to laparoscopy and laparoscopic ultrasonography, biopsy of all suspected lesions outside the area of potential resection., Main Outcome Measures: Number of patients in whom the findings obviated the need for exploratory laparotomy., Results: There were no complications related to the laparoscopy. The investigation showed distant metastases (which were histologically verified) in 11 patients (23%, 95% confidence interval (CI) 16 to 30). These patients had non-operative palliation. Seven were identified by laparoscopy, and laparoscopic ultrasonography showed the other four. In three patients whose distant metastases had already been identified by laparoscopy, ultrasonography was omitted. Three additional patients had suspect lesions, but these were not confirmed histologically. However, these lesions were shown to be cancerous at laparotomy. One additional patient had an intra-abdominal metastasis which was missed by laparoscopy with ultrasonography., Conclusions: Laparoscopy with ultrasonography safely detected metastases that had not been shown by conventional staging investigations in 23% of 48 patients with carcinoma of the gastric cardia. The investigation should therefore be added to the standard staging procedures in patients with carcinoma of the gastric cardia that is involving the distal oesophagus.

Objective: Development of a prognostic tool for patients with unresectable pancreatic cancer to distinguish between with low or high probabilities of survival 3 to 9 months after diagnosis., Design: Data about individual patients from five studies were pooled. A multivariate proportional hazards model with time-dependent covariates was developed, including age, sex, and metastases. An extended model was developed on a subset of patients, including weight loss, pain, and jaundice at diagnosis., Setting: Multicentre study, The Netherlands, Norway, USA, UK, and Canada., Subjects: 1020 patients with unresectable pancreatic cancer., Main Outcome Measures: Prediction of prognosis., Results: Patients with metastases, pain, or weight loss at diagnosis had a significantly poorer prognosis than the others. Older men had a worse prognosis than younger men, while older women had a better prognosis than younger ones. Patients with jaundice had a relatively good prognosis. Differences in survival among the studies were incorporated in a prognostic score chart., Conclusion: The prognostic score chart can be used to select patients with relatively low expectation of survival for endoscopic palliation, and patients with relatively high expectation for surgical palliation.