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The treatment for metastasised medullary thyroid cancer is still a topic of discussion. One of the main challenges remains to find effective adjuvant and palliative options for patients with metastatic disease. The diagnostic and treatment strategies for this tumour are discussed and possible new developments commented. Approaches that target rearranged during transfection (RET) are preferable to those that target RET downstream proteins as, theoretically, blocking RET downstream targets will block only one of the many pathways activated by RET. Combining several agents would seem to be more promising, in particular agents that target RET with those that independently target RET signalling pathways or the more general mechanism of tumour progression.

Objective: Discussing prognosis is often confronting and complex for cancer patients. This study investigates bow patients' psychological characteristics relate to their preferences concerning the disclosure of prognosis. Methods: One hundred and seventy-six esophageal cancer patients participated in the study. They had undergone esophagectomy within the past 28 months and did not have evidence of cancer recurrence. Patients completed a questionnaire eliciting their preferences for prognostic information. Sociodemographic characteristics, involvement preferences, anxiety, depression, fear of recurrence, striving for quality of life (QOL) or quantity of life and trust in physicians were explored as predictors for (a) wanting to be informed about prognosis and (b) the initiation of discussion about prognosis. Results: Patients wanting all prognostic information had more fear for the disease to recur (p < 0.05) and were inclined to be more actively involved during consultation (p < 0.001). Post hoc analyses showed that patients with worse QOL scores reported more fear of recurrence. Anxiety, depression, trust and tendency to strive for QOL or quantity of life were not related to preferences concerning prognostic information. Conclusions: The more fear patients have for esophageal cancer to recur, the more information they want about prognosis. Thus, patient's fear for recurrent disease is not a reason for withholding prognostic information. Results also suggest that there is no harm in asking patients what information they want. Copyright (C) 2009 John Wiley & Sons, Ltd.

Background: The outcome of different palliative regimens was investigated in patients with incurable oesophageal carcinoma identified during surgical exploration. Patients and Methods: Between January 1992 and December 2002, 203 patients with oesophageal cancer underwent surgery after a standard staging procedure including computer tomography and endoscopic ultrasonography. The data from 78 patients, rendered incurable at exploration and who subsequently underwent palliative interventions, were analysed retrospectively. Results: The median survival in the whole group was 8.9 (1-105) months. Patients treated with chemotherapy had a higher median survival of 11.6 months compared with that of the other palliatively-treated patients: 8.4 months (p=0.003). Overall, intraluminal stenting was the palliative measure of dysphagia in 25 patients (32.3%). Conclusion: Patients with incurable oesophageal carcinoma have a poor overall survival of less than 9 months. Stenting is frequently (32%) needed for ultimate palliation of dysphagia after primary treatment. In a selective. group, palliative chemotherapy offered a survival benefit compared with othered treatment modalities.

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 FDG 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

OBJECTIVE. On PET, the level of tissue glycolysis can be quantified by the accumulation of fluorine-18-fluorodeoxyglucose expressed as the standardized uptake value (SUV). The aims of this study were to investigate the relation between SUV and the stage of disease and whether SUV can be used to predict resectability and survival in patients with esophageal cancer. CONCLUSION. SUV can be used to predict resectability; however, SUV is not an independent factor that can be used to assess survival in patients with esophageal cancer.

Because of improvements in diagnostic technology, the incidental detection of synchronous primary tumors during the preoperative work-up of patients with esophageal cancer has increased. The aim of this study was to determine the rate and clinical relevance of synchronous neoplasms seen on F-18-FDG PET in staging of esophageal cancer. Methods: From January 1996 to July 2004, 366 patients with biopsy-proven malignancy of the esophagus underwent F-18-FDG PET for initial staging. This series of patients was retrospectively reviewed for the detection of synchronous primary neoplasms. Results: Twenty synchronous primary neoplasms (5.5%) were identified in 366 patients. Eleven neoplasms were in the colorectum, 5 in the kidney, 2 in the thyroid gland, 1 in the lung, and 1 in the gingiva. One of the thyroid lesions and the lung lesion were erroneously interpreted as metastases, leading to incorrect upstaging of the esophageal tumor. Conclusion: F-18-FDG PET detected unexpected synchronous primary neoplasms in 5.5% of patients with esophageal cancer. Sites of pathologic F-18-FDG uptake should be confirmed by dedicated additional investigations before treatment, because synchronous neoplasms may mimic metastases.

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

Standard staging of esophageal and gastroesophageal junction (GEJ) tumors substantially lacks accuracy. The aim of this study was to investigate whether the addition of PET with F-18-FDG is a valuable gain in the initial staging. Methods: Between January 1996 and January 2002, F-18-FDG PET was performed in 74 patients. Conventional staging included CT in all patients and well-performed endoscopic ultrasonography (EUS) in 52 patients. They were compared with F-18-FDG PET with pathology and follow-up of suspicious lesions as the gold standard. Results: PET identified 70 primary tumors (sensitivity, 95%). Sensitivity to identify locoregional metastases was highest for EUS (69%) but was not different for CT and PET (44% and 55%, respectively). PET was able to identify distant nodal disease in 71% (17/24 patients) compared with 29% (7/24 patients) after combined CT/EUS alone (P = 0.021). Sensitivity to detect distant nodal and systemic (M1) disease increased with PET (78% vs. 37%; P = 0.012). PET upstaged 15 patients (15/74; 20%) correctly as M1 disease, missed by CT/EUS, and correctly downstaged 4 patients (5%) from M1 to MO disease. However, false upstaging and downstaging was encountered in 5 (7%) and 3 (4%) patients, respectively. Conclusion: PET improves the currently applied staging of esophageal and GEJ tumors, particularly by ameliorating the detection of M1 disease.

PURPOSE: The aim of this study was to determine the relationship between survival and value of molecular markers in the primary tumour in a group of patients with irresectable rectal cancer, treated with preoperative chemo-radiotherapy. MATERIALS AND METHODS: Immunohistochemistry for p53, p21, bcl-2 and Ki-67 was performed on pre-treatment biopsy specimens of 34 patients with irresectable rectal cancer. Preoperative treatment consisted of pelvic irradiation of 45-56 Gy, combined with 5FU and leucovorin (350/20 mg/m2 x 5 d; in weeks 1 and 5 during radiotherapy). The median follow-up was 38 months. Endpoints were pathological T-stage and survival after surgery. RESULTS: Expression of p21 correlated significantly with survival (p=0.005). Survival and p21 expression also correlated significantly, when adjusted for tumour response (p=0.005, RR=4.8 (1.6-14.7)). CONCLUSION: Expression of p21 predicts a worse survival in irresectable rectal cancer treated with preoperative chemo-radiotherapy. No relationship was found between tumour response in chemo-radiotherapy and p53, bcl-2 or Ki-67.

The purpose of the study was to analyse the prevalence of shoulder complaints after nerve sparing neck dissection at least I year after surgery, and to analyse the influence of radiation therapy on shoulder complaints. Patients were interviewed for shoulder complaints, and patients filled out the shoulder disability questionnaire to evaluate shoulder disability in daily activities. In total 137 patients; 51 after modified radical neck dissection (MRND), 21 after postero-lateral neck dissection (PLND), and 65 after supraomohyoid neck dissection (SOHND) were analysed. After MRND 33.3% of the patients experienced shoulder complaints, after PLND 66.7%, and after SOHND 20% of the patients experienced shoulder complaints. Type of neck dissection was significantly (P

Background: Cell cycle regulating proteins (p53/p21) and proliferation index Ki-67 have been associated with prognosis and response to chemotherapy. The aim of this study was to determine the significance of these molecular markers on tumor response and prognostic effect in a group of esophageal cancer patients treated with neoadjuvant chemotherapy. Patients and Methods: Immunohistochemical expression of p53/p21 and Ki-67 was examined in pretreatment biopsy specimen of 30 patients, in phase II neoadjuvant studies for locally advanced adenocarcinoma of the esophagus, who underwent surgery. Seven patients (23%) had progressive disease. Resection was achieved in all responders (n=23; 77%) and histochemical expression of the above-mentioned proliferating markers was examined in pre-treatment and resection specimens after chemotherapy. Results: Responders had a significantly better survival compared to non-responders (p=0.001). Expression of p53, p21 and high Ki-67 in pre-treatment specimens was 73% (22/30), 63% (19/30) and 30% (10/30), respectively and was not related to response to chemotherapy. However, alteration in expression of p53-positivity in the pre-treatment specimens to p53-negativity in the resection specimens and p21-negativity to p21-positivity in 6 of the 23 (26%) resected tumors was correlated with better response and survival (p=0.011). Conclusion: Data from this study showed that alteration of p53 and p21 expression rather than the initial expression seems to be related to chemotherapy response and overall survival in patients with esophageal adenocarcinoma.

Background: The clinical value and costs of different diagnostic tools used to identify potentially curable recurrent disease in patients treated adjuvantly for curatively resected Dukes' C colonic cancer were examined. Methods: The study group comprised 496 patients treated with chemotherapy over a I-year interval. Follow-up consisted of interim history, physical examination, liver ultrasonography or computed tomography (CT), measurement of carcinoembryonic antigen (CEA) levels, chest radiography and colonoscopy. Results: Two hundred and thirteen patients had recurrent disease (median follow-up 43 months). Forty-two patients with recurrence (20 per cent) mere treated with curative intent (median survival 38 months; 5-year survival rate 40 per cent). Recurrence was identified by liver ultrasonography or CT (n = 14), evaluation of symptoms (n = 12), colonoscopy (n = 8), CEA measurement (n = 3), chest radiography (n = 2), physical examination (n = 1) and other modalities in two patients. The mean cost of diagnostic procedures per curative resected recurrence for patients amenable to salvage surgery was US$9011. Of all treatable recurrences, 12 of 42 were identified by evaluation of symptoms only. Ultrasonography and colonoscopy identified 22 recurrences at a cost of US%11 790 per patient, while routine follow-up by CEA measurement, chest radiography and physical examination identified a further six at a cost of US$19 850 per patient. Conclusion: Potentially curable recurrences were detected primarily by liver imagining and colonoscopy. The yield of CEA measurement, chest radiography and physical examination was relatively low; such methods were expensive and should not be recommended in the routine follow-up of these patients.

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 mu m 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. (C)2000 American Cancer Society.

The aims of the study were to compare the value of L-[1-C-11]tyrosine (TYR) and [F-18]fluoro-2-deoxy-D-glucose (FDG) as tumor tracers in patients with breast cancer, to investigate the correlation between quantitative values and standardized uptake values (SUVs) and to estimate the value of SUVs for the evaluation of therapy. Methods: Eleven patients with one or more malignant breast lesions and two patients with one or more benign breast tumors were studied with TYR and FDG. Doses of 300 MBq of TYR and 230 MBq of FDG were given intravenously. All PET sessions were performed using a Siemens ECAT 951/31 camera. Of 10 malignant tumors and the 3 benign lesions, glucose consumption and protein synthesis rate were quantified. All lesions were studied using SUVs based on body weight, body surface area and lean body mass, with and without correction for plasma glucose or tyrosine levels. Results: All malignant tumors were visualized with both FDG and TYR, but the visual contrast was better with FDG, Increased uptake of the tracers was seen in patients with fibrocystic tissue and complicated the visual assessment and the outlining of tumor tissue. Uptake in fibrocystic disease was more prominent with FDG than with TYR. No difference in tumor/nontumor ratio between the two tracers could be established. FDG showed a false-positive result in one benign lesion. No major differences between the SUVs as defined above were found, although the best correlation between glucose consumption and the SUV was observed when the SUV was based on body surface area and corrected for plasma glucose level (r = 0.85-0.87). The SUV based on lean body mass was found to correlate best with protein synthesis rate (r = 0.83-0.94). Conclusion: in this group of patients, TYR appears to be a better tracer than FDG for breast cancer imaging, because of lower uptake in fibrocystic disease, SUVs correlate well with quantitative values, but future studies must determine whether treatment evaluation is also reliable with SUVs.

Between 1974 and 1993 ten girls and six boys aged patient had a slight increase in thyroglobulin levels 6-16 years underwent total thyroidectomy, with therapeutic selective neck dissection in six patients. All children were treated after operation with radioactive iodine (I-131) for ablation of thyroid tissue remnants. Papillary carcinoma occurred in ten patients, follicular carcinoma in two and medullary thyroid lesions in four. The patients were followed for a median of 11.5 (range l-20) years with regular determinations of serum thyroglobulin levels and I-131 whole-body scanning when indicated. Only one patient had a slight increase in thyroglobulin levels without evidence of disease on further screening. In children with medullary lesions the serum levels of basal and pentagastrin-stimulated calcitonin remained normal. currently all patients are alive and without disease. Hypocalcaemia lasting for more than 1 year was observed in one patient. Recurrent nerves were not injured accidentally, but because of tumour invasion two of 32 recurrent nerves had to be sacrificed. This surgical approach is safe and well tolerated in children.

For patients with gastric cancer deemed curable the only treatment option is surgery, but there is disagreement about whether accompanying lymph-node dissection should be limited to the perigastric nodes (D1) or should extend to regional lymph nodes outside the perigastric area (D2). We carried out a multicentre randomised comparison of D1 and D2 dissection. 1078 patients were randomised (539 to each group). 26 allocated D1 and 56 allocated D2 were found not to satisfy eligibility criteria (histologically confirmed adenocarcinoma of the stomach without clinical evidence of distant metastasis). Each of the remainder was attended by one of eleven supervising surgeons who decided whether curative resection was possible and, if so, assisted with the allocated procedure. Among the 711 patients (380 D1, 331 D2) judged to have curable lesions, D2 patients had a higher operative mortality rate than D1 patients (10 vs 4%, p=0.004) and experienced more complications (43 vs 25%, p While we await survival results, D2 dissection should not be used as standard treatment for western patients.

19 consecutive patients underwent a posterolateral neck dissection (PLND) in continuity with a wide excision of the primary melanoma on the posterior scalp. After a mean follow-up of 74 months, 5 patients are alive with minimal morbidity. PLND can safely be performed, even bilaterally, as an elective or therapeutic procedure in posterior scalp melanoma.