Search

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and antibodies against TRAIL receptors death receptor 4 (DR4) and death receptor 5 (DR5) are under investigation for cancer therapy. To study the potential application of these agents, the expression of DR4 and DR5 were studied immunohistochemically in colorectal adenomas and carcinomas from patients with sporadic disease (n = 74 and 56, respectively), familial adenomatous polyposis (FAP, n = 41 and 4, respectively) and hereditary non-polyposis colorectal cancer (HNPCC, n = 50 and 21, respectively). BAX, which is frequently mutated in tumours with high-frequency microsatellite instability (MSI-H) may play a role in sensitivity to TRAIL. Therefore, MSI-H carcinomas (n = 42, of which 27 sporadic and 15 HNPCC) were analysed for apoptotic activity, assessed by M30 immunoreactivity, and BAX mutations. Most adenomas from all three patient groups expressed DR4 and DR5. Most carcinomas expressed DR4, except for six cases, all with mucinous histology. All carcinomas, including mucinous carcinomas, showed DR5 expression. BAX mutations were found in 6/ 42 MSI-H cancers with similar apoptotic indices and expression of DR4, DR5 and TRAIL in BAX mutant and wild-type cases. Since most sporadic and hereditary colorectal neoplasms express DR4 and DR5, targeting of these receptors may be a potential prevention or treatment strategy. (c) 2005 Elsevier Ltd. All rights reserved.

Distant metastases or local invasion are frequently found during the explorative phase of surgery for esophageal cancer. This study was performed to determine the rate of patients with incurable disease encountered during exploration and to examine the impact of preoperative staging, including positron emission tomography (PET), on the number of unnecessary explorations. The records of 203 patients with esophageal cancer who were eligible for curative resection were retrospectively reviewed. The surgical reports were analyzed to obtain the reasons for abandoning resection. Furthermore, the different staging modalities according to the related time interval were reviewed for each patient to analyze the influence of them on the number of explorations. After exploratory surgery, resection was abandoned in 78 of the 203 patients (38%) because of distant metastases (n = 59; 29%), metastatic spread and local irresectability (n = 5; 2%), and local irresectability (n = 14; 7%). In a logistic regression model with all preoperative staging modalities and the year of examination as independent variables, F-18-fluorodeoxyglucose (FDG-PET) was the only modality that predicts intended curative resection in these patients (P

Heterogeneity in advanced colon cancer leads to different results from adjuvant chemotherapy. To identify groups of patients who may need adjuvant treatment, molecular staging and correlation with clinical data may be helpful in classifying histologically similar tumors. Colon cancer develops through a multistep process with an accumulation of multiple genetic alterations that are often the cause of a form of genomic instability. The 2 best known mechanisms of genomic instability are chromosomal instability (CIN) and microsatellite instability (MSI). The CIN phenotype is found in approximately 85% of sporadic colon cancers and is characterized by aneuploidy, multiple chromosomal rearrangements, and an accumulation of somatic mutations in oncogenes such as K-ras and tumor suppressor genes such as TP53 and APC. The MSI phenotype is associated with small insertions and deletions mainly in repetitive sequences (microsatellites) and is found in approximately 15% of cases. This instability, often referred to as high-frequency MSI (MSI-H), is caused by defects of the mismatch repair system, which is involved in repairing DNA errors that arise during DNA replication. Clear-cut correlations between the somatic genetic alterations in tumors and the clinical behavior of the tumor are rare. Only a few markers, such as MSI-H and TP53, seem to have a prognostic value. Mutations in the TP53 gene are associated with an aggressive tumor growth and subsequent reduced survival, whereas MSI-H seems to be correlated with a favorable outcome. In general, predicting biologic behavior of in particular stage III colon cancers is difficult and remains a great clinical problem.

Background. Secondary hyperparathyroidism can complicate renal replacement therapy (RRT) in patients with end-stage renal disease. Current medical therapies often result in hypercalcaemia and fail to correct hyperparathyroidism, but might be more effective at an early stage of disease. The aim of this study was to identify prognostic factors at the start and during the first year of RRT for refractory secondary hyperparathyroidism needing parathyroidectomy (PTx) during long-term follow-up.Methods. A total of 202 consecutive patients starting RRT between August 1988 and August 1996 at our centre with at least 1 year of follow-up were included. Biochemical and treatment data at the start and during the first year of RRT were collected. Univariate and multivariate analyses were used to identify risk factors for PTx during follow-up.Results. Thirty-three patients (16%) needed PTx after 52 +/- 23 months of RRT. Need for PTx was not different between patients undergoing haemodialysis and peritoneal dialysis, but was associated with parameters reflecting calcium and phosphate control at start and after 1 year of RRT. In a Cox multivariate model, serum parathyroid hormone [relative risk (RR): 1.02 per pmol/l; P Conclusions. Failure of control of calcium-phosphate metabolism at the start of and early during RRT is strongly associated with PTx during long-term follow-up. Given the high prevalence of insufficient phosphate control, patients may benefit from aggressive correction of serum phosphate in the pre-dialysis and early dialysis period.

Background: The optimal surgical treatment in children with well-differentiated thyroid carcinoma remains an important point of discussion. In this study, we evaluated our surgical experience and reviewed the literature accordingly to identify the most adequate treatment. Methods: We retrospectively analyzed 21 children, all under the age of 18 years at the time of diagnosis, with differentiated thyroid carcinoma (17 papillary, 3 follicular, and 1 Hurthle cell carcinoma). Total thyroidectomy was performed, followed by radioiodine therapy, as a part of the initial treatment in all patients. The results were compared with data from the literature. Results: Eleven children (52%) who presented with cervical lymph node metastases were treated by a modified radical neck dissection. Pulmonary metastases were seen at diagnosis in three patients. Six patients developed temporary complications. During follow-up, with a median of 11 years (range, 2–26 years), two patients (10%) developed recurrences, and no patient died during this observation period. A literature search confirmed our experience of excellent results without an increase of complications in the more aggressively treated patients. Conclusions: In children with differentiated thyroid cancer, treatment should consist of total thyroidectomy, followed by a modified radical neck dissection (when indicated) and iodine-131 ablation treatment. This aggressive approach seems to be justified because of the high incidence of nodal involvement and the low complication and recurrence rate after surgery.

147 Background: Involvement of the circumferential margin (CRM) is an important factor in esophageal cancer (EC) patients. CRM definitions are commonly based on the College of American Pathologists (CAP) at 0 mm and the Royal College of Pathologists (RCP) at >1 mm. We evaluated which CRM definition is useful in current practice with neoadjuvant chemoradiotherapy (CRT) and whether the CRM cut-off value differs after CRT. Methods: We prospectively included 209 patients (104 with CRT) with locally advanced EC (stage II-III), who underwent radical transthoracic esophagectomy. Patients were followed for at least 2 years after surgery or until death. Patients with 5cm), >0.2 L/N+ ratio, angioinvasion and CAP R0. In the surgery group; tumor length, >4 N+, angioinvasion and CAP R0 were independent prognostic factors (P

Item does not contain fulltext BACKGROUND: Surgery is still the only curative treatment for medullary thyroid cancer (MTC). We evaluated clinical outcome in patients with locoregional MTC with regard to adequacy of treatment following ATA guidelines and number of sessions to first intended curative surgery in different hospitals. METHODS: We reviewed all records of MTC patients (n = 184) treated between 1980 and 2010 in two tertiary referral centers in the Netherlands. Symptomatic MTC (palpable tumor or suspicious lymphadenopathy) patients without distant metastasis were included (n = 86). Patients were compared with regard to adequacy of surgery according to ATA recommendations, tumor characteristics, number of local cancer reoperations, biochemical cure, clinical disease-free survival (DFS), overall survival (OS), and complications. RESULTS: Adherence to ATA guidelines resulted in fewer cancer-related reoperations (0.24 vs. 0.60; P = 0.027) and more biochemical cure (40.9 vs. 20 %; P = 0.038). Surgery according to ATA-guidelines on patients treated in referral centers was significantly more often adequate (59.2 vs. 26.7 %; P = 0.026). Tumor size and LN+ were the most important predictors for clinical recurrence [relative risk (RR) 4.1 (size > 40 mm) 4.1 (LN+) and death (RR 4.2 (size > 40 mm) 8.1 (LN+)]. CONCLUSIONS: ATA-compliant surgery resulted in fewer local reoperations and more biochemical cure. Patients in referral centers more often underwent adequate surgery according to ATA-guidelines. Size and LN+ were the most important predictors for DFS and OS.

187 Background: Patients with curable esophageal cancer (EC) which proceed beyond the original CROSS eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect of extending the CROSS eligibility criteria for nCRT on treatment related toxicity and overall survival (OS) in EC. Methods: Included were 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0), treated with the CROSS schedule followed by esophagectomy. Group 1 (N = 90) consisted of patients which met the CROSS criteria and patients in group 2 (N = 71) met the extended eligibility criteria, i.e. including a tumor length of > 8 cm (N = 23), > 10% weight loss (N = 35), > 2 – 4 cm extension in the stomach (N = 21), celiac lymph node metastasis (N = 13), and/or age > 75 years (N = 2). We assessed the differences in hematologic toxicity (≥ grade 3) and 90-day postoperative mortality. Moreover, we assessed the prognostic value on OS with multivariate Cox regression analysis. Results: No difference was found in hematologic toxicity and 90-day mortality. The OS differed significantly (P = 0.003), with a median of 37.3 (95% CI 10.56 – 64.0) and 17.2 (95% CI 13.8 – 20.6) months in group I and II, respectively. Pathological N-stage (P = 0.024), ypT-stage (P = 0.044), and group II (P = 0.006) were independent prognostic factors for OS. Conclusions: Extension of the CROSS study eligibility criteria for nCRT did not affect hematologic toxicity and postoperative mortality, but was prognostic for OS.

111 Background: Although essential in treatment decision making, clinical nodal (cN) staging in esophageal cancer (EC) remains difficult. We assessed the rate of nodal up- and downstaging and its prognostic value on 5-year disease-free survival (DFS) in EC patients treated with surgery-alone or with neoadjuvant chemoradiotherapy (nCRT). Methods: For this retrospective study, we included 395 EC patients who underwent a curative esophagectomy with or without nCRT between 2000 and 2015. The surgery-alone and nCRT group were matched on clinical T-stage (cT), cN-stage, and histopathological type using propensity score matching ( n=270). Staging consisted of PET with CT, or PET/CT, and endoscopic ultrasonography (n = 235). We compared cN and pathological N-stage (pN) and scored correct, down- and upstaging. The prognostic value of nodal up- and downstaging and localization of node metastases on 5-year DFS were assessed with multivariate Cox regression analysis (factors with a P-value 25% nodal downstaging. This inaccuracy might impede assessment of true nodal response to nCRT, affording dubious decisions for a ‘wait-and-see’ strategy.

Background. Surgical management of recurrent pleomorphic adenoma of the parotid gland has a considerable risk of facial nerve injury and a high re-recurrence rate. To obtain more insight into this issue we evaluated our experiences. Methods. Medical records and histologic material of all these patients (31 women and 21 men), who had been treated from 1976-1995 were reviewed. Median interval between initial treatment and commencement of recurrences was 3 (0.8-18) years. Last surgery consisted of parotidectomy in 48 patients (92%), including 19 (40%) total procedures and wide local excision with involved skin in four patients. Results. At a median follow-up of 9 years, eight patients (8/52; 15%) had re-recurrences develop, including 4 of 21 patients (19%) after a previous parotidectomy (group I) and 4 of 31 patients (13%) without prior parotidectomy (group II). The chance of re-recurrence in a group of patients with a minimal follow-up of 10 years after salvage surgery was 17% (4 of 24). The risk of a new relapse was, respectively, 4% and 8% at 1 and 5 years after treatment of recurrent disease. Acceptable N.VII function was preserved in 45 of the 49 (92%) nerves at risk. The risk of N.VII injuy was higher and more serious in group I (29% vs 10% in group II). The function of tour of the five (80%) reconstructed zygomaticotemporal branches of the N.VII was adequate. Conclusion. Surgical treatment of recurrent pleomorphic adenoma of the parotid gland, usually consisting of a parotidectomy with wide extent and eventually facial nerve reconstruction, demonstrates favorable results with acceptable morbidity. The risk of new relapse and N.VII injury was higher after previous parotidectomy. (C) 2001 John Wiley & Sons, Inc.

Fanconi anemia (FA) is an autosomal recessive syndrome with a marked predisposition to malignancies, in particular acute myeloid leukemia and squamous cell carcinoma of the oral cavity. We examined oral squamous cell carcinoma tissue from two FA patients (FA-A and FA-C) by comparative genomic hybridization. Both tumors, which were negative for human papilloma as well as Epstein-Barr viral sequences, showed multiple alterations with a high proportion of whole-arm chromosomal gains and losses. This combination of features as well as the sites involved in chromosomal breakage are very similar to what is typically observed in non-FA oral tumors. These results suggest that the process leading to early occurrence of oral cancer in FA patients follows a similar pathway as in non-FA cancer patients, which would support a caretaker function for FA genes in the protection against oral carcinogenesis. Since FA patients are uniquely hypersensitive to DNA cross-linking agents, while oral cancer in the general population is thought to be environmentally induced, these results also suggest that environmental DNA cross-linkers may be causally involved in oral carcinogenesis.

BACKGROUND The sentinel lymph node biopsy (SLNB) is a diagnostic or staging option in the treatment of patients with cutaneous malignant melanoma (CMM) and is investigated intensively. A positive SLNB has appeared to identify patients who might have benefited from a lymph node dissection (LND). Intraoperative frozen section analysis (FSA) of the sentinel lymph node (SLN) during surgery would allow SLNB and LND to be performed in the same procedure. In the current study, we tested the reliability of FSA on the sentinel lymph node in patients with CMM. METHODS Before definitive treatment of their melanomas began, FSA was performed on the SLNBs of 58 patients, whose median age was 56 (22–81) years, and who were 55% male and 45% female. Serial sections (500 μm interval), stained with routine hematoxylin and eosin and immunohistochemistry (S-100 and HMB-45), obtained definitive histology of the sentinel lymph node. RESULTS Detection of the sentinel lymph node was possible in 56 patients (97%). Sixty-one SLNBs were performed in these patients. FSA detected metastases in 5 of 108 SLN (5%) in 5 patients. This was upgraded after definitive histology to 13 SLN (12%) in 11 patients (20%). Sensitivity of the FSA was 38%. After a median follow-up of 35 (range: 24–54) months, the false-negative rate of the SLN was 4% (2 patients). CONCLUSION The combination of the low sensitivity of FSA and a finding that only 12% of the SLNBs contained metastases does not justify routine use of FSA on the SLN of patients with CMM. Cancer 2000;89:1720–5. © 2000 American Cancer Society.

A comprehensive mutation detection assay is presented for the entire coding region and all splice site junctions of the KRAS oncogene. The assay is based on denaturing gradient gel electrophoresis and applicable to archival paraffin-embedded tumour material. All KRAS amplicons are analysed within two lanes of a DGGE gel under a single set of experimental conditions. Six known codon 12 mutations in genomic DNA from different paraffin-embedded tumours could readily be detected. When testing 35 paraffin-embedded Dukes' C colorectal carcinomas for unknown mutations, 12 tumours were found with mutations in codons 12 or 13. None of the tumours appeared to have a codon 61 mutation. In nine tumours, however, 11 additional sequence variations were found outside the hot-spot codons. None of these occurred in germline DNA from 57 individuals. Of these variations, three are considered as significant mutations, as they result in a non-conservative substitution of amino acid residues essential for the functioning of the KRAS protein. Thus, in total, 15 of the 35 Dukes' C tumours (43%) had a KRAS mutation of functional significance. Moreover, a novel exon 4B polymorphism was found to occur in 10 of the 35 tumours. The results of this study suggest that in restricting analysis of KRAS to hot-spot mutation sites only, significant information may be missed.

A comprehensive mutation detection assay is described for the entire coding region and all splice site junctions of TP53. The assay is based on denaturing gradient gel electrophoresis, which follows either multiplex polymerase chain reaction (PCR) applied to DNA extracted from fresh or frozen tissue samples or nested PCR applied to DNA extracted from paraffin-embedded tissue samples. in both instances, the analysis can be performed under a single set of conditions. when testing the assay on DNA from cultured lung cancer cell lines and from paraffin-embedded Dukes C colorectal carcinomas, significant TP53 mutations were observed at high frequencies in 15 of 16 lung cancer cell lines (94%) and in 21 of 30 paraffin-embedded tissue samples of Dukes C colorectal carcinomas (70%). A substantial proportion of these significant mutations occurred outside the evolutionary conserved region of TP53 in 4 of 16 lung cancer cell lines (25%) and in 11 of 30 paraffin-embedded colorectal carcinomas (37%). This underscores the importance of a comprehensive TP53 mutation analysis in those instances that TP53 mutation is taken into account for diagnostic and prognostic purposes.

Background The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. Methods This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients' RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. Findings 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6–13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0·57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339 patients with bilateral phaeochromocytoma who underwent surgery. However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who underwent adrenal-sparing surgery did not become steroid dependent. Interpretation The treatment of multiple endocrine neoplasia type 2-related phaeochromocytoma continues to rely on adrenalectomies with their associated Addisonian-like complications and consequent lifelong dependency on steroids. Adrenal-sparing surgery, a highly successful treatment option in experienced centres, should be the surgical approach of choice to reduce these complications. Funding European Union, German Cancer Foundation, Arthur Blank Foundation, Italian Government, Charles University, Czech Ministry of Health, Nanjing Military Command, National Science Centre Poland, National Research Council for Scientific and Technological Development, and State of São Paulo Research Foundation Fil: Sanso, Elsa Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina Fil: Barontini, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina

Postoperative pulmonary complications (PPCs) are the most commonly reported complications after esophagectomy. The aim of this study was to examine the effect and feasibility of preoperative inspiratory muscle training-high intensity (IMT-HI), and IMT-endurance (IMT-E) on the incidence of PPCs in patients following esophagectomy for esophageal cancer (EC).A single-blind, randomized, clinical pilot study was conducted between 2009 and 2012. Forty-five participants were assigned to either IMT-HI or IMT-E. Effectiveness was assessed by analyzing PPCs, length of hospital stay (LOS), duration of mechanical ventilation, stay on the intensive care unit, and number of reintubations. Maximal inspiratory pressure and lung function changes were recorded pre- and post-training. Feasibility was assessed by IMT-related adverse events, training compliance, and patients' satisfaction.Thirty-nine patients could be analyzed, 20 patients in the IMT-HI arm and 19 patients in the IMT-E arm. The incidence of PPCs differed significantly between groups and was almost three times lower for the IMT-HI group (4 vs. 11 patients; p = 0.015). Other differences in favor of the IMT-HI group were LOS (13.5 vs. 18 days; p = 0.010) and number of reintubations (0 vs. 4 patients; p = 0.030). Both interventions proved to be equally feasible.Preoperative IMT-HI showed to be a promising, effective, and feasible intervention to reduce PPCs in EC patients undergoing esophagectomy. Further research with a larger sample size is recommended.

To evaluate the rate and pattern of recurrences after neoadjuvant chemoradiotherapy (CRT) in esophageal cancer patients.We described survival and differences in recurrences from a single center between neoadjuvant CRT (carboplatin/paclitaxel and 41.4 Gy) and surgery alone for the period 2000-2011. To reduce bias, we performed a propensity score matched analysis.A total of 204 patients were analyzed, 75 treated with neoadjuvant CRT and 129 with surgery alone. The pathologic response to neoadjuvant CRT was 69 % with a complete response rate of 25 %. After matching, baseline characteristics between the groups (both n = 75) were equally distributed. The 3- and 5-year disease-free survival was 53 and 42 % in the neoadjuvant CRT group compared with 24 and 18 % in the surgery-alone group (P = 0.011). After 3 and 5 years' CRT, patients had an estimated locoregional recurrence-free survival of 83 and 73 % compared with 52 and 49 % in the surgery-alone group (P = 0.015). The distant recurrence-free survival was comparable in both groups. Locoregional recurrences were located less in the paraesophageal lymph nodes in the CRT group than in the surgery-alone group, 9 versus 21 %, respectively (P = 0.041). With respect to differences in distant recurrences, we observed more skeletal recurrences in the surgery-alone group compared to CRT, 12 versus 1 % (P = 0.009).The neoadjuvant CRT regimen we used offers a significant improvement in outcome, with a different recurrence pattern compared with surgery alone. This effect is probably due to both the pathologic complete response and eradication of micrometastases in CRT group.

Background & Aims Benign anastomotic strictures are often difficult to treat. We assessed the efficacy of adding corticosteroid injections to endoscopic dilation therapy with Savary bougienage. Methods In a multicenter, double-blind trial, 60 patients (mean age, 63 ± 9 years; 78% male) with an untreated cervical anastomotic stricture after esophagectomy with gastric tube reconstruction and dysphagia for at least solid food were randomly assigned to groups given 4 quadrant injections of 0.5 mL triamcinolone (40 mg/mL, n=29) or saline (controls, n=31) into the stricture, followed by Savary dilation to 16 mm. Dysphagia, complications, and quality of life were assessed after 1 and 2 weeks and 1, 3, and 6 months. The primary end point was a dysphagia-free period of 6 months. Results In the corticosteroid group, 45% of the patients remained dysphagia-free for 6 months, compared with 36% of controls (relative risk, 1.26; 95% confidence interval, 0.68–2.36; P = .46). Median time to repeat dilation was 108 days (range, 15–180 days) in the corticosteroid group vs 42 days (range, 17–180 days) for controls ( P = .11). A median number of 2 dilations (range, 1–7) was performed in the corticosteroid group vs 3 dilations (range, 1–9) in controls (relative risk, 0.76; 95% confidence interval, 0.42–1.38; P = .36). Two major intervention-related complications occurred, 1 submucosal laceration in the corticosteroid group and 1 hemorrhage in the control group. Four patients in the corticosteroid group, but none of the controls, developed Candida esophagitis ( P = .03). Conclusions Corticosteroid injections do not provide a statistically significant decrease in frequency of repeat dilations or prolongation of the dysphagia-free period in patients with benign anastomotic esophagogastric strictures. Dutch Trial Registration Number 2236.

131 Background: Surgery after neoadjuvant chemoradiotherapy (nCRT) is the most common treatment with curative intent for esophageal cancer (EC) patients. Definitive chemoradiotherapy (dCRT) is an alternative for patients who are not eligible for resection because of comorbidity. The purpose of this retrospective study was to evaluate patient and tumor characteristics which are associated with the type of treatment. Methods: We selected all consecutive patients with a locally advanced EC (cT1 N + / T2-3N0-3M0-1a) who were treated with curative intent (nCRT, dCRT or surgery only) in the South East Netherlands between 1995 and 2013. For a proper assessment of the impact of co-morbidity, T4 tumors were excluded. The effect of co-morbidity on treatment decision and on survival was analyzed using a multivariable logistic regression and Kaplan-Meier method. Survival time was defined as time from 6 months after diagnosis until death or until January 1st 2015 for patients who were still alive. Results: Of the 1098 patients, surgery only was performed in 46%, nCRT in 28% and dCRT in 26%. Patients with ≥ 2 co-morbidities underwent more frequently dCRT (OR = 2.35; 95% CI: 1.45-3.86), or resection only (OR = 2.29; 95% CI: 1.41-3.69). Patients > 75 years (OR = 6.66; 95% CI: 3.48-12.77), patients with hypertension and diabetes (OR: 4.05;95% CI: 1.96-8.37-3.90) and patients with cardiovascular (mostly myocardial infarction) and pulmonary comorbidity (OR = 3:33; 95% CI: 1:51 to 7:34) underwent frequently more dCRT than nCRT. Patients with esophageal squamous cell carcinoma (ESCC) also had more frequently dCRT (OR = 2.27; 95% Cl: 1.38-3.73). Patients with an adenocarcinoma and ≥ 2 co-morbidities had favorable 3-year overall survival (OS) after nCRT compared with dCRT and surgery alone (p < 0.01). However, the 3-year OS after nCRT was similar after dCRT in ESCC patients with ≥ 2 co-morbidities (p = 0.75). Conclusions: The results of this study support the treatment with dCRT in patients with SCC of the esophagus, and with at least two co-morbidities, in particular, the combination of cardiovascular / pulmonary disorders and hypertension plus diabetes.

25 Background: The optimal sequence of endoscopic ultrasonography (EUS) and positron emission tomography with computed tomography (PET/CT) in esophageal cancer (EC) is a matter of debate. The use of EUS with fine needle aspiration (FNA) after PET/CT seems to increase the efficacy of curative intended neoadjuvant or definitive chemoradiotherapy. Retrospectively, we assessed the impact of EUS in the PET/CT upfront model on the treatment decision making in EC patients. Methods: In the period 2009 to 2015, 298 EC patients were staged with hybrid PET/CT or PET with CT, and EUS if applicable, in a non-specific order to assess curability (T1-4a,N0-3M0). We determined the feasibility of EUS and whether the initial or additional EUS changed the primary decision suspicious incurable (T4b and M+) into curable disease or added extra nodal information leading to up/downstaging or exhibit suspected nodes at different lymph node stations. In addition, we assessed if EUS changed the radiation area (i.e. lymph nodes > 3.5 cm from the defined radiation target volumes) in the PET/CT “upfront model”. Results: EUS was complete in 185 (62.1%) and incomplete due to stricture from a relative obstructing tumor in 59 (19.8%) patients. Fifty-four patients (18.1%) did not receive EUS because of stenosis (n = 46; 15.4%), patient dependent reasons (n = 4; 1.3%) or other reasons (n = 4; 1.3%). EUS after hybrid PET/CT or PET with CT (n = 244) gave additional information in 166 patients (68.0%); it changed the curability in 4 (1.6%), lead to nodal up and downstaging in respectively, 81 (33.2%) and 27 (11.1%) patients, changed the number of or lymph node station of suspected lymph nodes in an additional 58 patients (n = 23.8%), and FNA gave additional information in 34 (13.9%) patients. EUS after PET/CT ”upfront” changed the treatment plan in 90 patients (36.9%), including alteration in the radiation field (86; 35.2%) and curability (4; 1.6%). Conclusions: EUS gave additional information after PET/CT “up front” and altered the radiation field in about one third of the EC patients, suggesting a better yield of “EUS on indication” after PET/CT upfront.

Background. Neoadjuvant chemoradiotherapy (CRT) improves locoregional control and overall survival in esophageal cancer patients. Although adverse events are relatively low during neoadjuvant CRT, severe postoperative adverse effects may occur, leading to morbidity and even mortality. We investigated the impact of a more frequently used neoadjuvant CRT regimen of 41.4 Gy/5 weeks radiotherapy with concurrent carboplatin and paclitaxel (CROSS schedule) on the postoperative course.Methods. Between 2006 and 2012, a total of 96 esophageal cancer patients (staged cT1N+/T2-4a/N0-3 and M0) were treated according to the above neoadjuvant scheme. To reduce bias in this single-center study, we performed a propensity score-matched analysis with patients who underwent surgery alone (n = 230) from a prospectively maintained database (n = 326).Results. Baseline characteristics between both groups were equally distributed in the matched cohort. In the neoadjuvant treated group, significantly more patients were diagnosed with pneumonia (27.1 vs. 51.0 %; p = 0.001), pleural effusion (12.5 vs. 24.0 %; p = 0.040), and arrhythmia (20.4 vs. 34.4 %; p = 0.008). In addition, in the multivariate analysis, neoadjuvant CRT was significantly associated with an increased risk of pneumonia (p = 0.001, odds ratio 2.896), pleural effusion (p = 0.041, odds ratio 2.268), and arrhythmia (p = 0.023, odds ratio 2.215). Despite these outcomes, no differences were detected in duration of intensive care unit or hospital stay. Short-term mortality did not differ between both groups.Conclusions. We observed an increase of cardiopulmonary complications in the neoadjuvant CRT group, without any effect on hospital or intensive care unit stay and mortality. Further research is warranted on the limitation of chemoradiation-induced cardiopulmonary toxicity.

The molecular alterations underlying follicular Hürthle cell carcinomas (FHCCs) are largely unknown. In an attempt to clarify this issue, we analysed a series of Hürthle cell tumours for the presence of RET/PTC and PAX8/PPARG rearrangements and BRAF, HRAS and NRAS mutations.We investigated a series of 20 follicular Hürthle cell tumours [17 FHCCs and three follicular Hürthle cell adenomas (FHCAs)]. RET/PTC rearrangements were found in 33% of FHCAs and in 38% of FHCCs. All RET/PTC-positive FHCCs had a solid pattern of growth. PAX8/PPARG rearrangement was present in 27% of the FHCCs which displayed, in most cases, a follicular architecture. NRAS mutation was detected in one FHCC. An FHCC with a solid/microfollicular growth pattern scored positive for both RET/PTC and PAX8/PPARG rearrangement.Our study has shown a significant association between RET/PTC rearrangements and FHCCs with a solid growth pattern, thus raising the possibility of using tyrosine kinase inhibitors for the treatment of patients with FHCCs, which are often refractory to radioiodine treatment.

Background The prognostic significance of primary tumor location, especially the poor prognosis for melanomas in the scalp and neck region, is well established. However, the prognosis for different sites of nodal macrometastasis has never been studied. This study investigated the prognostic value of the location of macrometastasis in terms of recurrence and survival rates after therapeutic lymph node dissection (TLND). Methods All consecutive FDG-PET-staged melanoma patients with palpable and cytologically proven lymph node metastases operated at our clinic between 2003 and 2011 were included. Disease-free survival and disease-specific survival (DSS) were compared for nodal metastases in the groin, axilla, and neck regions by multivariable analysis. Results A total of 149 patients underwent TLND; there were 70 groin (47 %), 57 axillary (38 %), and 22 neck (15 %) dissections. During a median follow-up of 18 (range 1–98) months, 102 patients (68 %) developed recurrent disease. Distant recurrence was the first sign of progressive disease in 78, 76, and 55 % of the groin, axilla, and neck groups, respectively (p = 0.26). Low involved/total lymph nodes (L/N) ratio (p

136 Background: The main objective of this study was to develop and validate a method to reconstruct the gross and clinical tumor volume (GTV and CTV) on the esophageal specimen in order to facilitate a good pathologic examination of the original tumor area after neo-adjuvant chemoradiation (CRT). Methods: The GTV and CTV borders of 25 patients were defined by a radiation oncologist on the planning CT in relation to 5 anatomical reference points. After CRT, the GTV and CTV borders were marked in vivo on the esophagus during surgical resection. Finally, the pathologist evaluated the presence of macroscopic and microscopic tumor in- and outside the GTV and CTV. The radiation tumor response was scored according to the standardized 5-tier Mandard classification. Radiation induced side effects were scored as well. Results: The Mandard classification could be scored on basis of the GTV alone in 68% of the cases (N=17). For the other patients (N=8), the GTV and the CTV should both be incorporated for correct evaluation of the tumor response. Five patients (20%) showed complete tumor response (Mandard 1), 68% (N=17) showed partial response (Mandard 2-3) and 12% (N=3) showed hardly any response (Mandard 4-5). In the partial responders, macroscopic tumor was found within the delineated GTV and microscopic tumor remained within the CTV both in 100% of the cases. In two patients (40%) with hardly any response, microscopic tumor was also found outside the CTV. This might be caused by tumor growth during the neo-adjuvant treatment or by geographical miss. Nine patients turned out to have positive lymph nodes. On average 18 (range 8-30) lymph nodes were evaluated per patients. Giant cell reactions, lymphocyte infiltration, and fibrosis, which indicate tumor regression were seen in the CTV and GTV, and were most pronounced in the GTV. Conclusions: This study suggested that demarcation of the GTV and CTV on the esophagus in vivo is important for standardized pathologic evaluation of the esophagus after neo-adjuvant chemoradiation. Furthermore using this method we determined microscopic tumor outside the CTV in 40% of the cases (N=2) of the bad responders (Mandard 4-5), illustrating the importance of our method in this patient category.

BACKGROUND: Parathyroid carcinoma is a rare malignancy and generally is diagnosed after surgery for primary hyperparathyroidism. Lack of a preoperative diagnosis and ill-considered surgical planning with its impact on survival are ill-described.METHODS: In a retrospective population-based cohort study the clinical features, treatment, recurrences, and survival of 41 parathyroid cancer patients are reported and compared with characteristics of patients with primary hyperparathyroidism.RESULTS: Patients with parathyroid carcinoma had significantly higher serum parathyroid hormone and calcium levels compared with patients with primary hyperparathyroidism. Nineteen patients (46%) had a palpable neck mass. A parathyroid hormone level more than 3 times the upper normal limits was suspicious and levels more than 10 times carried a positive predictive value of 84% for carcinoma. Ten-year recurrence-free and disease-specific survival rates were 71% and 79%, respectively.CONCLUSIONS: Parathyroid hormone levels of more than 3 times upper normal limits, palpable neck mass, and profound hypercalcemia are suspicious signs of carcinoma necessitating surgical exploration by an experienced surgeon. (C) 2011 Elsevier Inc. All rights reserved.

Medullary thyroid cancer (MTC) has a variable clinical presentation. We present 3 patients with this endocrine tumour. The first patient, a 41-year-old woman complaining of diarrhoea, a painful abdomen, weight loss and sensibility disorders in both legs, had metastases of MTC in the spine, with little progression during 2 years of follow-up. The second patient, a 64-year-old woman suffering from a painful nodule in the neck and a painful shoulder, was diagnosed with MTC and liver, lung and bone metastases. She died after 14 months due to progressive disease. The third patient, an 81-year-old woman with hyperparathyroidism, was coincidentally diagnosed with MTC after goitre surgery at the age of 67. When she was evaluated for rising calcitonin levels, a pheochromocytoma was found. RET mutation analysis confirmed a MEN2A syndrome. Current diagnostic procedures of MTC may include positron emission tomography with 18F-deoxyglucose (FDG-PET) and 18F-diphenylalanine (DOPA-PET). MTC is usually treated surgically. Tyrosine kinase inhibitors appear to offer potential new therapeutic possibilities.

BACKGROUND: Different risk-prediction models have been developed, but none is generally accepted in selecting patients for esophagectomy. This study evaluated 5 most frequently used risk-prediction models, including the American Society of Anesthesiologists, Portsmouth-modified Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM), and the adjusted version for Oesophagogastric surgery (O-POSSUM), Charlson and the Age adjusted Charlson score to assess postoperative mortality after transthoracic esophagectomy.METHODS: Data were obtained from 278 consecutive esophageal cancer patients between 1991 and 2007. Performance in predicting postoperative mortality (in-hospital and 90-day mortality) were analyzed regarding calibration (Hosmer and Lemeshow goodness-of-fit test) and discrimination (area under the receiver operator curve).RESULTS: The Hosmer and Lemeshow goodness-of-fit test was applied to each model and showed a significant outcome for only the P-POSSUM score (P = .035). The receiver operator curve indicated discriminatory power for P-POSSUM (.766) and for O-POSSUM (.756), other models did not exceed the minimal surface of .7.CONCLUSIONS: Postoperative mortality after esophagectomy was best predicted by O-POSSUM. However, it still overpredicted postoperative mortality. (C) 2011 Elsevier Inc. All rights reserved.

The present study evaluated the efficacy and safety of oxaliplatin, UFT, and leucovorin in metastatic gastric cancer.Patients received intravenous oxaliplatin 130 mg/m(2) on day 1, followed by oral UFT capsules (350 mg/m(2) per day) and leucovorin tablets (90 mg/day), every 8 h, for 14 days, in a 3-week cycle.Twenty-three patients (61% with a parts per thousand yen2 metastatic sites), median age of 60 years (range, 39-69 years) were entered. Based on intention-to-treat analysis, one complete response and seven partial responses were found, resulting in an overall response rate (RR) of 35% (95% confidence interval [CI], 16-54), a median time to progression of 4 months (95% CI, 0.5-7.5), and a median overall survival (OS) of 8 months (95% CI, 4.5-11.5). The 1-year survival rate was 26%. Three patients did not complete the first course of 2 weeks; 1 died suddenly on day 16 with fatal lung embolism; 1 had rapid progressive disease and 1 experienced gastric hemorrhage on day 15 - both these patients withdrew. In the 20 patients assessable for toxicity no grade 4 toxicity occurred, grade 3 toxicity consisted of anemia in 1, diarrhea in 2, and neurotoxicity in 3 patients. No hand-foot syndrome (HFS) occurred.Oxaliplatin is an effective drug in gastric cancer, but, as previously reported, its feasibility in combination with capecitabine is hampered due to combined hand-foot-based toxicity. The present phase II study of a combination of oxaliplatin with UFT and leucovorin appears to have efficacy and tolerability comparable to two other drug regimens used in gastric cancer, without the HFS problem.

Despite declining incidence and improved surgical care, gastric cancer remains associated with high mortality. Incidence and survival show remarkable geographic differences. Japanese patients have a much better chance of cure than Western patients. Whether biological differences between Japanese and Western patients are responsible for this remains unclear. Japanese surgeons, however, generally use a different surgical approach. The so-called R2 resection for gastric cancer has been investigated in a number of retrospective trials and, even in the West, evidence is accumulating that a more extensive resection of lymph nodes might positively influence stage dependent survival rates. Whether this approach indeed improves treatment and not just influences staging is currently being studied in a nation-wide, prospective randomized trial in the Netherlands. The design and the first results of this trial are presented here.

BACKGROUND: High recurrence rates determine the dismal outcome in esophageal cancer. We reviewed our experiences and defined prognostic factors and patterns of recurrences after curatively, intended transthoracic esophagectomy.METHODS: Between January 1991 and December 2005, 212 consecutive patients underwent a radical transthoracic esophagectomy with extended 2-field lymphadenectomy. Recurrence rates, survival, and prognostic factors were analyzed (minimal follow-up period, 2 y).RESULTS: Radicality was obtained in 85.6%. The median follow-up period was 26.6 months. The overall recurrence rate at I, 3, and 5 years was 28%, 44%, and 64%, respectively, and locoregional recurrence rate was 17%, 27%, and 43%, respectively. Overall survival rates, including postoperative deaths, were 45% and 34% at 3 and 5 years, respectively. pT stage and lymph node (LN) ratio greater than .20 were independent prognostic factors for survival and recurrences. Radicality was most prognostic for survival, and for N+ greater than 4 positive LN for recurrences.CONCLUSIONS: Radicality and LN ratio are strong prognostic factors. High radicality and adequate nodal assessment are guaranteed by an extended transthoracic approach. (C) 2010 Elsevier Inc. All rights reserved.

PURPOSE: The impact of the reported number of lymph nodes at pathologic examination of colon specimens on survival was studied.METHODS: The data of 2,281 patients with localized colon cancer were retrospectively reviewed. The effect of tumor characteristics and surgical and pathologic factors on the number of lymph nodes and examined lymph node numbers on nodal status and survival were analyzed.RESULTS: The number of examined nodes increased with T stage, left-sided tumors, and mucinous morphology, but decreased with age. The proportion of node-positive patients increased with a larger number of nodes. A high number of examined nodes and high T stage affected nodal status. The five-year overall survival was 51.3 percent for node-positive patients vs. 68.2 percent for node-negative patients. Node-negative patients had a significantly higher five-year crude and relative survival when more lymph nodes were examined. This was not found for the node-positive group and for all patients combined.CONCLUSIONS: T stage, localization, and patient age were predictive for the number of nodes examined. A higher number of examined nodes was associated with an increase in node positivity. The survival benefit can be explained by stage migration. Eventually this may lead to an overall survival benefit, as more patients are classified as node-positive, and therefore will receive adjuvant therapy.

Background: Selective embolization therapy (SET) has been employed to treat a number of malignant tumors, but experience with its use in metastatic epithelial thyroid carcinoma (ETC) is limited. Here we report our experience with the effect of SET on symptoms and serum thyroglobulin (Tg) in patients with bone metastases from ETC.Methods: This was a retrospective study of 13 patients with bone metastases from ETC who underwent 65 embolizations for bone metastases in 43 sessions. In the treated patients, symptoms considered related to bone metastases were compared before and about 4-7 weeks after the embolization session. Embolization sessions were excluded for analysis if concomitant therapy had taken place within 4-7 weeks before and/or after the session. Serum Tg concentrations were employed as an index of tumor debulking by SET. We attempted to estimate the influence of SET on survival time in patients with disseminated ETC who did, and an historical control group of patients with disseminated ETC who did not receive SET.Results: After exclusion of 12 (of which 3 sessions failed) out of 43 sessions, clinical symptoms, such as pain, and neurological symptoms decreased after 17, increased after 6, and did not change after 8 procedures. In 43 sessions, 20 of which were excluded (including the 3 sessions that failed), serum Tg decreased after 14 and increased after 9. The median standardized survival time of the group that received embolization was not significantly different to that of the group that did not receive embolization.Conclusions: Embolization therapy does not appear to improve life expectancy, but in selected patients can achieve palliation of pain, prevent neurological damage, reduce tumor burden, and give devascularization of the tumor before surgery.

Background and study aims: To assess the prognostic importance of standardized uptake value (SUV) for 18F-fluorodeoxyglucose (FDG) at positron emission tomography (PET) and of EUS parameters, in esophageal cancer patients primarily treated by surgery.Patients and methods: Between October 2002 and August 2004 a prospective cohort study involved 125 patients, with histologically proven cancer of the esophagus, without evidence of distant metastases or locally irresectable disease based on extensive preoperative work-up, and fit to undergo major surgery. Follow-up was complete until October 2006, ensuring a minimal potential follow-up of 25 months.Results: The median SUV was 0.27 (interquartile range 0.13-0.45), and was used as cutoff valuebetween high (n=62) and low (n=63) SUV. Patients with a high SUV had a significantly worse disease-specific survival compared with patients with a low SUV (P = 0.04). Tumor location (P =0.005), EUS T stage (P Conclusion: In esophageal cancer patients, EUS T stage, EUS N stage, location and SUV of the primary tumor are pretreatment factors that are associated with disease-specific survival. However, only EUS T stage is an independent prognostic factor.

We aim to determine the effect of splenectomy on clinical outcome in patients with cancer of the distal esophagus and gastro-esophageal junction (GEJ) after a curative intended resection. From January 1991 to July 2004, 210 patients underwent a potentially curative gastroesophageal resection with an extended nodal dissection. The study group was divided into: group I with splenectomy, consisting of 66 patients (31.4%), and group II without splenectomy, of 144 patients. Splenectomy was performed for oncological reasons. Medical records were reviewed retrospectively. Postoperative complications occurred in 27 patients (40.9%) in group I and in 68 patients (47.2%) in group II (P = 0.4). The overall mortality was not significantly different between both groups (P = 0.7). There was a higher administration of red blood cells during surgery (P < or = 0.001), increased operating room (OR) time (P < or = 0.001) and longer intensive care unit (ICU) stay (P = 0.01) in group I. Independent prognostic factors for survival were outcome of surgery, nodal metastases, gender, complications and ICU stay. Sepsis was a strong prognostic factor among the complications. The 1 and 2-year survival was significantly higher in group II; 75% and 67% (P = 0.032) compared to 69% and 56% (P = 0.017) in group I, respectively. However, the 5-year survival was not different in both groups (29% in group I and 60% in group II, P = 0.191). Splenectomy had no marked effect on mortality and morbidity after curative resection of esophageal cancer. Splenectomy had a significant increase in blood transfusions with prolonged OR time and ICU stay and decreased short-term survival.

Contains fulltext : 70883.pdf (Publisher’s version ) (Open Access) ABSTRACT: BACKGROUND: Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer. METHODS/DESIGN: Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score).Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy). DISCUSSION: The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice. TRIAL REGISTRATION: ISRCTN45750457.

Purpose. To find out if single-photon emission computed tomography (SPECT) and I-123-subtraction can enhance the findings of Tc-99-methoxyisobutylisonitrile (MIBI) scintigraphy for the preoperative localization of parathyroid (PT) tumors.Methods. Among the 111 consecutive patients who underwent preoperative planar Tc-99-MIBI scintigraphy for hyperparathyroidism (HPT), 64 underwent delayed SPECT, and 17 underwent I-123-subtraction. Two independent blinded experts scored the topographical localization, diagnostic confidence, and impact of each diagnostic modality on the surgical strategy.Results. For adenomas, Tc-99-MIBI scintigraphy had a sensitivity of 77% with a positive predictive value (PPV) of 83%. SPECT did not affect the sensitivity or PPV, but it increased the diagnostic confidence and changed the surgical strategy in 21% of the patients. I-123-subtraction increased the sensitivity from 64% to 82%, but decreased the PPV from 88% to 82%. In hyperplastic glands, Tc-99-MIBI scintigraphy had a sensitivity of 47% and a PPV of 95%. When Tc-99-MIBI scintigraphy was combined with SPECT and I-123-subtraction, the results were 44%/10% and 52%/92%, respectively. Both SPECT and I-123-subtraction decreased the diagnostic confidence.Conclusions. Adding SPECT to Tc-99-MIBI scintigraphy improved the surgical decision for parathyroid adenomas. The addition of I-123-subtraction was of limited value. For hyperplastic glands, Tc-99-MIBI scintigraphy was relatively ineffective, even with the addition of SPECT or I-123-subtraction.

Aim: Oesophageal cancer is highly lethal with a 5-year relative survival of 10-15%. An increasing incidence has been reported for several parts bf the Western world. We studied time trends in incidence, mortality and survival for oesophageal cancer in the Netherlands during 1989-2003.Methods: Data on incidence and survival were obtained from the Netherlands Cancer Registry and mortality data from Statistics Netherlands.Results: The age standardised incidence increased by 3.4% (p Conclusion: Oesophageal carcinoma incidence is rising in the Netherlands. Mortality increased at a slightly lower pace due to improving survival. (C) 2007 Elsevier Ltd. All rights reserved.

Purpose: To evaluate the value of external ultrasonography (US) of the neck in current dedicated preoperative staging of patients with cancer of the esophagus and gastroesophageal junction (GEJ).Materials and methods: We analyzed 180 consecutive patients (154 men, 26 women, and mean age 63 (38-84) years) without palpable cervical lymphadenopathy, treated between January 2001 and March 2006. Suspicious lesions were confirmed by cytological examination. All first 125 consecutive patients (group A) were staged by standard endoscopic ultrasonography (EUS), multidetector computed tomography (md-CT), positron emission tomography with F-18-fluorodeoxyglucose (FDG-PET) and external US. The other 55 patients (group B) were prospectively staged according to a revised protocol consisting of routine EUS and md-CT, while PET was only performed in subjects with T3-T4 and/or N1 disease and external US solely on indication.Results: Cervical metastases were found in seven patients from group A (6%) and in five from group B (9%). Twenty percent (4/20) of the tumors above the carina and 5% (8/160) of the distal tumors presented with cervical metastases. All were diagnosed as T3 and T4 tumors on EUS. Eleven of these metastases were detected by external US and nine on md-CT. All nodal metastases were detected by the combination of PET and md-CT. No cervical metastases were missed by the diagnostic algorithm in group B.Conclusion: In present staging procedures for esophageal cancer, routine external US seems to have no additional value in detecting cervical metastases. It is still indicated to obtain cytological proof of suspected cervical lesions. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Background. Extent of neck dissection is contro- versial in patients with palpable medullary thyroid cancer (MTC). Methods. We evaluated 64 MTC patients (19 hereditary, 45 sporadic) with palpable thyroid nodules (group 1, n ¼ 35) or pal- pable lymph node metastases (group 2, n ¼ 29). Standard sur- gery included total thyroidectomy, central compartment dissec- tion, and additional neck dissection on indication. Results. In group 1, 40% of the patients were cured. Thirty- one percent of all patients had central, 23% ipsilateral, 14% contralateral, and 14% mediastinal, metastases. Fifty-one per- cent developed locoregional recurrence. Locoregional recur- rence (p ¼ .043) and reoperations (p ¼ .020) were noted more often after a less than standard initial procedure. In group 2, no patients were cured. All had central, 93% ipsilateral, 45% con- tralateral, and 52% mediastinal metastases. Thirty-eight percent developed locoregional recurrence. Conclusions. Locoregional recurrence frequently occurs in palpable MTC, and tumor control may be improved by standard central, bilateral, and upper mediastinal neck dissection. V C 2007 Wiley Periodicals, Inc. Head Neck 29: 857-863, 2007

Background. The purpose of this retrospective study was to determine the long-term effects of radiotherapy on hearing function in patients who underwent parotidectomy and postoperative radiotherapy for unilateral tumors of the parotid gland.Methods, An extensive set of tests was used to measure hearing loss. The mean dose on middle ear, cochlea, and Eustachian tube was estimated with a CT-planning system.Results. A hearing loss of >= 15 dB in 3 frequencies was found in 32% of the 52 patients included in the study. Patients with an asymmetrical hearing loss received a higher mean dose on the hearing structures (p Conclusions. Radiation-induced hearing loss is a common complication. A mean dose of > 50 Gy on the cochlea should be avoided. (c) 2006 Wiley Periodicals, Inc.

The RET gene encodes a receptor tyrosine kinase that is expressed in neural crest-derived cell lineages. The RET receptor plays a crucial role in regulating cell proliferation, migration, differentiation, and survival through embryogenesis. Activating mutations in RET lead to the development of several inherited and noninherited diseases. Germline point mutations are found in the cancer syndromes multiple endocrine neoplasia (MEN) type 2, including MEN 2A and 2B, and familial medullary thyroid carcinoma. These syndromes are autosomal dominantly inherited. The identification of mutations associated with these syndromes has led to genetic testing to identify patients at risk for MEN 2 and familial medullary thyroid carcinoma and subsequent implementation of prophylactic thyroidectomy in mutation carriers. In addition, more than 10 somatic rearrangements of RET have been identified from papillary thyroid carcinomas. These mutations, as those found in MEN 2, induce oncogenic activation of the RET tyrosine kinase domain via different mechanisms, making RET an excellent candidate for the design of molecular targeted therapy. Recently, various kinds of therapeutic approaches, such as tyrosine kinase inhibition, gene therapy with dominant negative RET mutants, monoclonal antibodies against oncogene products, and nuclease-resistant aptamers that recognize and inhibit RET have been developed. The use of these strategies in preclinical models has provided evidence that RET is indeed a potential target for selective cancer therapy. However, a clinically useful therapeutic option for treating patients with RET-associated cancer is still not available.

Background. Various studies have demonstrated that 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET), measuring altered tissue glucose metabolism, is a promising non-invasive method for detecting both distant nodal and haematogenous metastases in patients with oesophageal carcinoma (OC) and might thus prevent futile oesophagectomies. Moreover, FDG-PET is a promising tool in assessing response to non-surgical treatment, and might therefore be used for an early decision on whether treatment should be stopped or continued. Material and methos. Review of the recent literature regarding the diagnostic performance of FDG-PET in the preoperative staging of patients with OC and regarding diagnostic accuracy of FDG-PET in assessing response to neoadjuvant therapy in patients with OC compared to conventional techniques (especially computed tomography (CT) and endoscopic ultrasonography (EUS)). Results. A search of the literature resulted in the inclusion of 16 studies on the diagnostic value of FDG-PET. Sensitivity and specificity for the detection of locoregional metastases were moderate. Sensitivity and specificity were reasonable for distant metastases. The diagnostic accuracy of FDG-PET in assessing response to treatment was similar to the accuracy of EUS, but significantly higher than that of CT. Conclusions. The staging value of FDG-PET in OC patients is limited in the detection of locoregional metastases; however; its value is higher in the detection of distant lymphatic and haematogenous metastases. Moreover, FDG-PET is a valuable tool for the non-invasive assessment of histopathologic tumour response after neoadjuvant therapy.

Background and Objectives: In the head and neck region, value, reliability, and safety of sentinel lymph node biopsy (SLNB) have not yet been determined conclusively. The aim of study was to assess impact of SLNB on disease outcome in cutaneous head and neck melanoma. Methods: Thirty-six patients with a clinically node-negative head and neck melanoma, >= 1.0 mm Breslow thickness, participated in a prospective study from 1995 to 2005. Sentinel lymph node (SLN) tumor-positive patients underwent completion lymphadenectomy. SLN tumor-negative patients underwent clinical monitoring. Median follow-up was 54 (range 10-114) months. Recurrence-free and overall survival curves were constructed by Kaplan-Meier. Results: SLNs could be identified in 33 patients (92%). In 7 patients (21%) the SLN was tumor-positive. In 1 patient (13%) the SLNB was false-negative. In 17 patients (47%) SLNs could be identified in the parotid region (success rate parotid region 100%). This study showed no significant difference in recurrence-free and overall survival between patients with tumor-positive and tumor-negative SLN. Conclusions: The safety and accuracy of SLNB in the neck and parotid nodal basins were similar to those in non-head and neck sites. However, the technique is technically demanding in this region. In this small series SLNB did not alter disease outcome.

Esophageal cancer development after previous atresia repair is extremely rare in young patients. We present the clinical course of a patient who developed an adenocarcinoma of the esophagus at the age of 22 years, after repair of a tracheoesophageal fistula with esophageal atresia in the neonatal period. She developed a stricture of the esophageal anastomosis requiring frequent dilatations. Six years after an antireflux procedure because of a difficult treatable severe gastroesophageal reflux, an advanced adenocarcinoma was detected at the site of the end-to-end anastomosis of the previous atresia. (c) 2005 Elsevier Inc. All rights reserved.

PURPOSE: To compare diagnostic accuracy of computed tomography (CT), endoscopic ultrasonography (US), and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for assessment of response to neoadjuvant therapy in patients with esophageal cancer by using a systematic review of the literature. MATERIALS AND METHODS: MEDLINE and EMBASE databases and Cochrane Database of Systematic Reviews were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. Summary receiver operating characteristic (ROC) analysis was used to summarize and compare the diagnostic accuracy of the three modalities. RESULTS: Four studies with CT, 13 with endoscopic US, and seven with FDC PET met inclusion criteria. Percentages of the maximum score in regard to methodological quality ranged from 15% to 100%. Summary ROC analysis could be performed for three studies with CT, four with endoscopic US, and four with FDG PET. The maximum joint values for sensitivity and specificity were 54% for CT, 86% for endoscopic US, and 85% for FDG PET. Accuracy of CT was significantly lower than that of FDG PET (P < .006) and of endoscopic US (P < .003). Accuracy of FDG PET and that of endoscopic US were similar (P = .839). In all patients, CT was always feasible, whereas endoscopic US was not feasible in 6% of the patients, and FDG PET was not feasible in less than 1%. CONCLUSION: CT has poor accuracy for assessment of response to neoadjuvant therapy in patients with esophageal cancer. Endoscopic US and FDG PET have equivalent good accuracy, but endoscopic US is not always feasible after chemotherapy and radiation therapy. FDG PET seems to be a promising noninvasive tool for assessment of neoadjuvant therapy in patients with esophageal cancer.

A 55-year-old man presented with weight loss and diffuse bone pain. Strongly elevated concentrations of calcium (3.49 mmol/L, with normoalbuminuria) and parathyroid hormone (260 pmol/L) indicated primary hyperparathyroidism.F-FDG PET/CT scanning demonstrated uptake in the right upper and right lower pole of the thyroid region but also multiple F-FDG-avid osteolytic lesions, including the 7th cervical and 3rd lumbar vertebrae (a). Histopathological examination of a vertebral bone biopsy revealed a brown tumour. An enlarged left upper and right upper parathyroid gland were resected using a sestamibi gamma probe. In addition, a left-sided hemithyroidectomy with ipsilateral paratracheal nodal dissectionwas performed because of a suspected mass in the left thyroid lobe and enlarged lymph nodes [1]. Pathological examination demonstrated a parathyroid adenoma but no carcinoma. Postoperative recovery was complicated by a severe hungry bone syndrome. Repeat FFDG PET/CT scanning 4 months after surgery showed a marked reduction in the number of F-FDG-avid lesions in the skeleton (b). Also the intensity of F-FDG uptake in the remaining lesions was significantly lower. Severe parathyroid bone disease is nowadays rarely encountered [2]. Brown tumours are osteolytic lesions which may mimic skeletal metastasis [3–5]. Microscopically, excessive osteoclast resorption is seen with destruction of cortical bone and formation of fibrous cysts. The marrow may be replaced by vascularized fibrous tissue and osteoclast-like giant cells. Haemosiderin deposits give these tumours their characteristic brown colour. Reduction in abnormal F-FDG uptake paralleled resolution of the hungry bone syndrome in our patient. Indeed, brown tumours may disappear after successful parathyroidectomy [5].

BACKGROUND Findings of mediastinal uptake of 131I after surgical treatment for differentiated thyroid carcinoma (DTC) are common, especially in young patients. Given the frequency of false-positive findings, a protocol for diagnostic and therapeutic strategies would be useful. With the goal of accurately selecting management strategies, the authors analyzed their data and data found elsewhere in the literature for correlations with the incidence of mediastinal 131I uptake and with treatment for patients exhibiting such 131I uptake. METHODS All patients with DTC who were treated between 1978 and 2000 at Groningen University Hospital (Groningen, The Netherlands) and who received adjuvant 131I ablation therapy were included in the current analysis, which involved retrospective review of all relevant data. RESULTS Five hundred four patients with DTC initially underwent total thyroidectomy, with additional 131I ablation performed for 489 of these patients. In 48 of 489 patients (9.8%), 131I uptake was seen in the mediastinum on a posttreatment scan. Analysis of those 48 patients and of cases in the literature demonstrated that serum thyroglobulin levels, risk status, and the presence of thymus on radiologic images were important in the surgical decision-making process. CONCLUSIONS Mediastinal uptake of 131I on posttreatment scans was found in approximately 10% of patients after total thyroidectomy for DTC. Based on the current data and the data presented in the literature, the authors developed a flow chart for determining appropriate treatment strategies, which included mediastinal dissection for high-risk patients and for patients with serum thyroglobulin levels > 10 ng/mL. Cancer 2005. © 2004 American Cancer Society.

Background and Study Aims: Endoscopic ultrasonography (EUS) is the most accurate method of assessing the locoregional extent of cancer of the esophagus and esophagogastric junction. The aim of this study was to evaluate the influence of tumor-related factors such as length and location on the accuracy of EUS in staging these tumors. Patients and Methods: Between January 1997 and September 2002, 280 consecutive patients underwent preoperative EUS for staging cancer of the esophagus and esophagogastric junction. The influence of histopathology, the presence of Barrett's dysplasia or stenosis, and the location and length of the primary tumor on the accuracy of EUS for T, N, and M staging were studied. Results: The overall accuracy rates of EUS for assessing the T, N, and M stages were 73%, 80%, and 78%, respectively. The influence of the tumor's histopathology and the presence of Barrett's dysplasia or stenosis was minimal. The accuracy of EUS was greater in tumors 5 cm or less in size than in tumors larger than 5 cm (82 % vs. 52 % for the T stage, P

Background. Studies on morbidity of the neck after head and neck cancer therapy are scarcely described. Methods. Patients who underwent surgery, including neck dissection, with and without radiation therapy at least 1 year before the study were asked to participate. We assessed neck pain, loss of sensation, range of motion of the cervical spine, and shoulder pain. Results. Of the 220 patients who were invited, 153 (70%) participated in the study. Neck pain was present in 33% of the patients (n = 51), and shoulder pain was present in 37% of the patients (n = 57). Neuropathic pain of the neck was present in 32% (n = 49); myofascial pain, in 46% (n = 70); and joint pain, in 24% (n = 37). Loss of sensation of the neck was present in 65% (n = 99) and was related to type of neck dissection and radia- tion therapy. Range of motion of the neck was significantly decreased because of the neck dissection and/or radiation therapy in lateral flexion away from the operated side. Conclusions. The occurrences of morbidity of the neck after cancer therapy were considerable and consisted of neck pain, loss of sensation, and decreased range of motion. A 2004 Wiley Periodicals, Inc. Head Neck 26: 785-791, 2004