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Introduction: Cachexia and obesity have been suggested to be risk factors for postoperative complications. However, high body mass index (BMI) might result in a higher R0-resection rate because of the presence of more fatty tissue surrounding the tumor. The purpose of this study was to investigate whether BMI is of prognostic value with regard to short-term and long-term outcome in patients who undergo esophagectomy for cancer. Methods: In 556 patients who underwent esophagectomy (1991-2007), clinical and pathological outcome were compared between different BMI classes (underweight, normal weight, overweight, obesity). Results: Overall morbidity, mortality, and reoperation rate did not differ in underweight and obese patients. However, severe complications seemed to occur more often in obese patients ( p = 0.06), and the risk for anastomotic leakage increased with higher BMI (12.5% in underweight patients compared with 27.6% in obese patients, p = 0.04). Histopathological assessment showed comparable pTNM stages, although an advanced pT stage was seen more often in patients with low/normal BMI ( p = 0.02). A linear association between BMI and R0-resection rate was detected ( p = 0.02): 60% in underweight patients compared with 81% in obese patients. However, unlike pT-stage ( p < 0.001), BMI was not an independent predictor for R0 resection ( p = 0.12). There was no significant difference in overall or disease-free 5-year survival between the BMI classes ( p = 0.25 and p = 0.6, respectively). Conclusions: BMI is not of prognostic value with regard to short-term and long-term outcome in patients who undergo esophagectomy for cancer and is not an independent predictor for radical R0 resection. Patients oncologically eligible for esophagectomy should not be denied surgery on the basis of their BMI class. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluated the Physiological and Operative Severity Score for the enUmeration of Mortality adjusted for oesophagogastric surgery (O-POSSUM). It analyzed data on patients who underwent oesophagectomy in a center for adenocarcinoma or squamous cell carcinoma of the oesophagus. Results showed that 24 patients died in hospital and the predicted ratio for in-hospital mortality was 0.29. It was concluded that O-POSUUM overpredicted in-hospital mortality threefold.

The article presents a study which assessed the additional value of fluorodeoxyglucose positron emission tomography (FDG-PET) after a state-of-the-art preoperative staging protocol. Suspicious hot spots in 30 patients were revealed by FDG-PET. Hot spots in seven patients appeared to be synchronous neoplasms. It was concluded that FDG-PET improves the selection of patients with oesophageal cancer for potentially curative surgery.

Introduction: For treatment of oesophageal cancer, neo-adjuvant locoregional hyperthermia (HT) has been applied in combination with chemotherapy (ChT) ± radiotherapy (RT) at the institute. Until now, 26 patients were treated within a completed phase I study combining HT with ChT and 29 patients within an ongoing phase II study combining HT with ChT + RT.Methods: HT was given with the 70 MHz AMC-4 waveguide system. Initially, oesophageal temperatures were measured using multi-sensor thermocouple probes (TCs) inside a nasogastric tube (NT), but the question arose whether these measurements were reliable enough to quantify the achieved tumour temperatures accurately. Presently, TCs are mounted on the outside of an inflatable balloon catheter (BC) for better intra-luminal fixation and better contact with the tumour. During 14 treatment sessions in four patients TCs inside a NT and mounted on a BC were used simultaneously. Data from these 14 treatment sessions were used to compare temperature and Specific Absorption Rate (SAR) measurements (‘ΔT-measurements’) using NTs or BCs. To determine the predictive value of the local SAR for the tumour temperatures achieved during treatment, the relation between the initial ΔT and steady state temperature (SST) was evaluated.Results: There was a strong correlation between the temperature measured in the NT (Ttube) and the temperature measured with a BC (Tballoon): R = 0.88 ± 0.13. However, Ttube was on average &nvsim;1°C higher than Tballoon and there was a large variation between the different treatments in the relation between both measurements, rendering Ttube a probably unreliable measure for tumour temperatures. The correlation between the ΔT measured in the NT (ΔTtube) and with a BC (ΔTballoon) was rather weak: R = 0.46 ± 0.25. The correlation between the initial ΔT and the SST was much stronger for the BC measurements, R = 0.78 ± 0.19, than for the NT measurements, R = 0.61 ± 0.23. Thus, ΔTballoon has a higher predictive value for the achieved tumour temperatures than ΔTtube. Both ΔT and SST were generally higher for the NT measurements than for the BC measurements, suggesting an over-estimation of tumour temperatures. Averaged over all treatments in the phase I trial using a NT (20 treatments) or a BC (45 treatments), T90 was significantly higher when measured with a NT.Conclusion: Oesophageal temperature and SAR (ΔT) measurements inside a NT are less reliable than BC measurements. These artefacts are due to bad thermal contact with the tumour tissue and are, therefore, not specific for thermocouple thermometry. For reliable temperature or SAR measurements inside lumina or cavities good thermal contact must be assured, e.g. by using a balloon catheter. [ABSTRACT FROM AUTHOR]

This phase I-II study investigated the feasibility of external deep loco-regional hyperthermia in localized primarily operable carcinoma of the thoracic oesophagus and gastro-oesophageal junction. Toxicity when combining neo-adjuvant hyperthermia with concurrent chemotherapy (CDDP and etoposide) was evaluated. Hyperthermia was given with a four antenna array, operating at 70 MHz arranged around the thorax. Temperatures were monitored rectally, intra-oesophageal at tumour level and intramuscular near the spine. In four steps, a thermal dose escalation was performed from 15-60 min of heating to 41°C with two patients in each step. The combined treatment courses were repeated every 3 weeks for a maximum of four courses. From January 1999-February 2002, 31 patients were included. Pre-treatment tumour stage mainly consisted of T3N1 (stage III) tumours, with a mean length of 6 cm. The maximum tumour temperature failed to reach at least 41°C in five patients during the test session of hyperthermia alone. Combined hyperthermia and chemotherapy was given 55 times in 26 patients. The amplitude was set at a ratio between top:bottom:left:right = 1:3:3:3, with a power range of 800-1000 W. Thermal data showed that is was technically feasible to heat the oesophagus; the median results were T 90 = 39.3°C, T 50 = 40°C, T 10 = 40.7°C and a median T max = 41.9°C. In more distally located tumours higher temperatures were reached. In one patient, a transient grade 2 sensory neuropathy was seen. Further toxicity was mainly of haematological origin. Blisters or fat necrosis were not observed. Twenty-two patients underwent oesophageal-cardia resection with gastric tube reconstruction. There was no report of complications in the post-operative phase, which could be contributed to either the prior chemotherapy or the hyperthermia. [ABSTRACT FROM AUTHOR]

Anti-Yo-associated paraneoplastic cerebellar degeneration is a cancer-related syndrome affecting the nervous system. This syndrome occurs almost exclusively in middle-aged women with gynecological cancers and it is rarerly found in patients with other types of cancer or in males. In this report we describe a male patient adenocarcinoma of the gastroesophageal junction and PCD with anti-Yo antibodies. To our knowledge, this is only the third report of PCD with positive anti-Yo antibodies in an esophageal tumor and the first report in a tumor of the gastroesophageal junction. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air–fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process. [ABSTRACT FROM AUTHOR]

Background Neoadjuvant chemoradiotherapy (nCRT) induces a pathologically complete response in approximately 30% of patients with oesophageal cancer. To explore the possibility of safe postponement of surgery, accurate clinical response evaluations are needed to exclude residual disease. The present study aims to assess the value of F-18-FDG-PET/CT for the detection of residual tumour (> 10% tumour cells = TRG3–4 vs. no vital cells = TRG1) or metastases after nCRT. Methods FDG-PET/CT at baseline and 12 weeks after nCRT was performed according to the European Association of Nuclear Medicine guidelines 1.0 (2.3MBq/kg F-18-FDG; scanning 60 ± 5min.) and the protocol of the preSANO study. Qualitative analysis included sensitive reading of presence of residual tumour and/or metastases. A lesion was considered FDG-positive, when any uptake in the lesion itself was above the adjacent oesophageal background uptake. Quantitatively, SUV/lean body mass (SUL) measurements at tumour, lymph nodes, oesophagus, liver and bloodpool were recorded and compared with pathology (resection specimen: gold standard). Results Some 129 of 207 patients with FDG-avid tumours at baseline proceeded to FDG-PET/CT at around 12 weeks after nCRT just before surgery. Forty-one of 129 patients had TRG3–4, of whom 6 were missed on FDG-PET/CT (15% false negative) with SULmax 2.07 ± 0.25, SUL-ratio tumour/oesophagus (SULR) 1.35 ± 0.14. Sensitivity for TRG2–3-4 vs. TRG1 was 57/71 (80%). SULmax and SULR of FDG-positives were 3.76 ± 1.33 and 1.82 ± 0.69 respectively, compared to SULmax 2.21 ± 0.42 and SULR 1.31 ± 0.22 in FDG-negatives. Distant metastases were detected in 18 of 190 (10%) patients. Of all patients with postponed surgery, 12 had ≥ 1 additional FDG-PET/CT during follow-up (25–49.7 weeks after nCRT). Eventually, 4 patients underwent surgery. Three of 4 had increased FDG-signal and TRG3–4; 1 patient had decreased FDG-signal and no tumour left (TRG1). Conclusion FDG-PET/CT at around 12 weeks after nCRT misses TRG3–4 tumours in 15% and detects residual TRG2–3-4 in 80%. Furthermore, PET-CT detects distant metastases in 10% of patients after nCRT. These data indicate that serial FDG-PET may become valuable in an active surveillance approach. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background An optimal model for predicting pathologic response after neoadjuvant chemoradiotherapy (nCRT) in oesophageal cancer has not been defined yet. FDG-PET/CT is frequently used in response assessments. The aim of this side study of the preSANO trial (NL41732.078.13) was to investigate if the FDG-PET parameters SUVmax, total lesion glycolysis (TLG) and metabolic tumour volume (MTV) were predictive for residual tumour in the resected specimen of oesophageal cancer patients treated with nCRT. Methods Patients underwent FDG-PET/CT at baseline according to the European Association of Nuclear Medicine guidelines 1.0 (2.3MBq/kg F-18-FDG; scanning 60 ± 5min.). All parameters were corrected for lean body mass. MTV was defined as the volume within a 41% of SULmax ( = SUV/lean body mass) isocontour threshold at tumour and lymph nodes. TLG was calculated as SULmean x MTV. Logarithmic transformation was performed because of non-normal distribution of TLG and MTV. Baseline PET parameters were compared to tumour regression grade in the resection specimen (TRG3–4 = > 10% residual tumour vs. TRG1 = complete response). Peroperatively irresectable tumours were recoded as TRG4. Analyses were performed using an independent-samples T-test. Results From a total of 207 patients who underwent FDG-PET/CT before nCRT, 197 were included for analysis (5 were non-FDG avid, 5 had incomplete data). Histological type of tumour: adenocarcinoma (AC) n = 154, squamous cell carcinoma (SCC) n = 42, and one adenosquamous carcinoma. Thirty-seven patients (19%) had TRG1 and 41 patients (21%) had TRG3–4. In complete responders (TRG1), SULmax, TLG and MTV (mean ± SD) were 9.6 ± 5.8, 85.3 ± 85.5 and 13.0 ± 9.9, respectively. In patients with TRG3–4, SULmax, TLG and MTV were 9.4 ± 5.4145.8 ± 164.6 and 21.9 ± 16.2, respectively. SULmax was not significantly different between both groups (P  = 0.8), but log(TLG) and log(MTV) (P  = 0.008 and P  = 0.001) were. In adenocarcinomas, log(TLG) did not differ between groups (P  = 0.1). Conclusion Initial FDG tumour mass, expressed as MTV, (rather than SULmax) is the most contributing factor in predicting residual disease after nCRT in both SCC and AC. The effect is stronger in SCC. Therefore, baseline FDG tumour mass should be included in a prediction model, besides other clinical and tumour parameters. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background An active surveillance approach has been proposed for patients with a clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (SANO trial). To justify renouncing surgical resection, patients with residual disease after nCRT should be accurately identified. However, substantial residual disease (TRG3–4) cannot be detected in 10% of patients with current diagnostic tests (preSANO trial). Circulating cell free tumor DNA (ctDNA) potentially improves detection of residual malignancy after nCRT and could be used for disease monitoring. The objective of this study was to investigate the feasibility of using ctDNA as biomarker for disease status after nCRT in esophageal cancer. Methods Twelve typical patients from the preSANO trial with variable pathological responses to nCRT were included. Blood was drawn and processed pretreatment. The feasibility of detecting TP53 mutations in baseline tumor biopsies was investigated using a next generation sequencing (NGS) panel. Subsequently, baseline blood samples of patients in whom specific TP53 mutations could be identified in baseline tumor biopsies or the surgical resection specimen were analyzed for ctDNA using cell free DNA NGS kits with single molecule barcoding (Oncomine Thermo Fisher). Results Baseline biopsy samples were available in 8 out of 12 patients. In 7 of these 8 patients (88%) specific TP53 mutations could be identified in their baseline biopsies. In 11 out of 12 patients (92%) specific TP53 mutations could be identified in baseline biopsies or the resection specimen. Eight of these 11 mutations were potentially detectable by the Oncomine panel. The panel detected TP53 mutational ctDNA in 4 of these 8 samples (50%). Conclusion Specific and clonal TP53 mutations can be identified in pretreatment biopsy samples and in surgical resection specimens of patients with esophageal cancer. These mutations can be matched to ctDNA identified in blood samples. Hence, ctDNA analyses in blood samples can potentially be used for disease monitoring during active surveillance and for disease monitoring in follow-up after surgical resection. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]