Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients.

BACKGROUND: At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. METHODS/DESIGN: In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. DISCUSSION: This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. TRIAL REGISTRATION: ClincalTrials.gov: NCT02243735 .

Accuracy and reproducibility of 3D-CT measurements for early response assessment of chemoradiotherapy in patients with oesophageal cancer.

BACKGROUND: Chemoradiotherapy is increasingly applied in patients with oesophageal cancer. The aim of the present study was to determine whether 3D-CT volumetry is able to differentiate between responding and non-responding oesophageal tumours early in the course of neoadjuvant chemoradiotherapy. PATIENTS AND METHODS: Serial CT before and after two weeks of neoadjuvant chemoradiotherapy was performed in the multimodality treatment arm of a randomised trial including patients with oesophageal carcinoma. CT response was measured with the change in tumour volume between baseline and after 14 days of neoadjuvant therapy. Receiver Operating Characteristic (ROC) analysis was used to evaluate the ability of 3D-CT as an early imaging marker of response. RESULTS: CT response analysis was performed in 39 patients, of whom 26 patients were histopathological responders. Median tumour volume increased between baseline and after 14 days of chemoradiotherapy in histopathological responders as well as in non-responders, though changes were not statistically significant. The area under the ROC curve was 0.71. CONCLUSION: Tumour volume changes after 14 days of neoadjuvant chemoradiotherapy as measured by 3D-CT were not associated with histopathological tumour response. CT volumetry should not be used for early response assessment in patients with potentially curable oesophageal cancer treated with neoadjuvant chemoradiotherapy.

FDG-PET parameters as prognostic factor in esophageal cancer patients: a review.

BACKGROUND: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been used extensively to explore whether FDG Uptake can be used to provide prognostic information for esophageal cancer patients. The aim of the present review is to evaluate the literature available to date concerning the potential prognostic value of FDG uptake in esophageal cancer patients, in terms of absolute pretreatment values and of decrease in FDG uptake during or after neoadjuvant therapy. METHODS: A computer-aided search of the English language literature concerning esophageal cancer and standardized uptake values was performed. This search focused on clinical studies evaluating the prognostic value of FDG uptake as an absolute value or the decrease in FDG uptake and using overall mortality and/or disease-related mortality as an end point. RESULTS: In total, 31 studies met the predefined criteria. Two main groups were identified based on the tested prognostic parameter: (1) FDG uptake and (2) decrease in FDG uptake. Most studies showed that pretreatment FDG uptake and postneoadjuvant treatment FDG uptake, as absolute values, are predictors for survival in univariate analysis. Moreover, early decrease in FDG uptake during neoadjuvant therapy is predictive for response and survival in most studies described. However, late decrease in FDG uptake after completion of neoadjuvant therapy was predictive for pathological response and survival in only 2 of 6 studies. CONCLUSIONS: Measuring decrease in FDG uptake early during neoadjuvant therapy is most appealing, moreover because the observed range of values expressed as relative decrease to discriminate responding from nonresponding patients is very small. At present inter-institutional comparison of results is difficult because several different normalization factors for FDG uptake are in use. Therefore, more research focusing on standardization of protocols and inter-institutional differences should be performed, before a PET-guided algorithm can be universally advocated.

The persisting presacral sinus after anastomotic leakage following anterior resection or restorative proctocolectomy.

AIM: Despite improvements in anastomotic technique, anastomotic leakage is frequently encountered following anterior resection. This can eventually evolve into a presacral sinus. This study assessed the incidence, the natural course and the outcome of persisting presacral sinus. METHOD: Patients who underwent low anterior resection (LAR) for cancer or restorative proctocolectomy (RPC) for ulcerative colitis or familial polyposis were eligible. Patients with anastomotic leakage or a presacral abscess were included. Outcome parameters included a persistent presacral sinus, or its closure and average time to closure and the stoma closure rate. RESULTS: Twenty-five patients were identified with a sinus after LAR (n = 20) or RPC (n = 5). A persistent sinus was present in nine (1%) of 834 patients after LAR and two (0.9%) of 229 patients after RPC. Definitive resolution of the sinus occurred in 12 (52%) of 23 assessable patients. This was achieved at a median of 340 days (range 23-731 days). At final follow-up, nine of the 23 patients had permanent faecal diversion because of recurrent abscess or persistent sinus formation, seven after LAR and two after RPC. CONCLUSION: A significant proportion of patients with anastomotic leakage after rectal surgery develop a chronic sinus, of which only half heal over time. Persisting sinus is the main reason for a permanent stoma.

Additional value of external ultrasonography of the neck after CT and PET scanning in the preoperative assessment of patients with esophageal cancer.

INTRODUCTION: Lymphatic dissemination of a (non-cervical) esophageal tumor to the neck is generally considered as distant metastasis. The aim of this study was to determine the additional value of external ultrasonography (US) to detect lymphatic metastasis to the neck after normal CT scan (CT) with or without normal PET scan (PET). METHODS: Between January 2003 and December 2005, 306 patients were analyzed for esophageal cancer in our department. A total of 233 patients underwent both CT and external US of the neck. PET was performed in 109 of these patients as part of a prospective cohort study. Fine needle aspiration (FNA) was only performed if external US reported suspected lymph nodes. FNA was defined as gold standard. RESULTS: In 176 patients (76%), CT did not identify any suspected nodes, but external US disagreed in 36 of them. In 9 of these patients, FNA confirmed metastasis, resulting in an additional value of external US after normal CT scanning of 5% (9/176). In 74 patients (68%), CT and PET did not identify any suspected nodes, but external US disagreed in 11 of them. In 3 of these patients, FNA confirmed metastasis, resulting in an additional value of external US after normal CT and PET of 4% (3/74). CONCLUSION: Considering its minimal invasiveness and wide availability in combination with the importance of the potential therapeutic consequences, we conclude that external US of the neck should be part of the routine diagnostic work-up in patients with esophageal cancer, even after normal CT and PET scanning.

Short and long-term advantages of transhiatal and transthoracic oesophageal cancer resection.

Two major surgical strategies to improve survival rates after oesophagectomy for oesophageal cancer have emerged during the past decades; (limited) transhiatal oesophagectomy and (extended) transthoracic oesophagectomy with two-field lymphadenectomy. This overview describes short and long-term advantages of these two strategies. In the short term, transhiatal oesophagectomy is accompanied by less morbidity. In the long term, this strategy is only preferable for patients with tumours located at the gastro-oesophageal junction, without involved lymph nodes in the proximal compartment of the chest. For patients with tumours located in the oesophagus, the transthoracic route with extended lymphadenectomy is probably preferred, because of improved long-term survival.

Importance of fluorodeoxyglucose-positron emission tomography (FDG-PET) and endoscopic ultrasonography parameters in predicting survival following surgery for esophageal cancer.

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 value between 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 < 0.001), EUS N stage (P = 0.006) and clinical stage (P < 0.006) were also associated with disease-specific survival. However, in multivariate analysis only EUS T stage appeared to be of independent prognostic significance (P = 0.007). 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.

[The value of positron emission tomography in the diagnosis and treatment of oesophageal cancer]. / De waarde van positronemissietomografie bij de diagnostiek en behandeling van het oesofaguscarcinoom.

Fludeoxyglucose positron emission tomography (FDG-PET) is a noninvasive imaging technique that applies the glucose metabolism to visualise the metabolic activity ofa tumour. FDG-PET might improve the selection of potentially curable patients with oesophageal cancer in addition to state-of-the-art conventional work-up (e.g. endoscopic ultrasonography and spiral CT). The additional value however is only 4% for all patients, and 7% in patients with stage III-IV disease. Moreover, the additional costs of FDG-PET are not compensated by the cost reduction ofprevented surgery. To improve the outcome of patients with oesophageal cancer the value ofneoadjuvant chemo- and/or radiotherapy is being investigated. FDG-PET seems to be a promising tool for the early assessment of response to neoadjuvant therapy. In case of non-response the ineffective neoadjuvant therapy can be stopped without further delaying appropriate surgery. FDG-PET might be able to improve the prediction of prognosis, in addition to commonly used histopathological factors.

Predictive factors associated with prolonged chest drain production after esophagectomy.

After esophagectomy, pleural drainage is performed to ensure complete drainage of the pleural cavities. The aim of this study was to detect predisposing factors for prolonged drainage. Patients who underwent transhiatal or extended transthoracic esophagectomy for adenocarcinoma of the distal esophagus or gastroesophageal junction were included. Patients who underwent esophagectomy produced a median total drainage volume of 2477 mL (range 30-14,908). Seventy-five patients needed chest drainage = 7 days (short drainage) while 57 patients needed chest drainage > 7 days (prolonged drainage). Factors associated with prolonged drainage were a transthoracic approach (P < 0.001), a higher volume of blood loss (P = 0.027), a higher number of resected lymphnodes (P = 0.046) and a radical dissection (P = 0.033). Prolonged pleural drainage is associated with a transthoracic approach and is seen more often in patients after a microscopically radical dissection. Prolonged drainage is a sign of adequate dissection on the site of the primary tumor, probably due to the more extensive trauma to the lymphatic vessels in the mediastinum.

Compartimentalization for chylothorax originating from the abdomen after extended esophagectomy. Report of two cases and review of the literature.

BACKGROUND: Chyle leakage from the chest after extended esophagectomy originating from the abdomen is a rare complication with various clinical presentations and treatments. METHODS: Two cases of chylothorax originating from the abdomen are discussed and the literature concerning diagnosis, management and outcome is reviewed. RESULTS AND CONCLUSION: Initially conservative measures should be installed; however, prolonged conservative treatment should be avoided. Reoperation gives an opportunity to identify the leak. If the leakage originates from the abdomen, compartimentalization is the essential step to solve the problem.