The Miscellaneous Mystery of Esophageal Cancer: New pathogenetic and clinical insights

Esophageal cancer is the 8th most common type of malignancy and the 6th most common cause of cancer mortality in the world. Worldwide more than 400,000 patients are newly diagnosed with esophageal cancer each year. The majority of patients (>90%) is diagnosed with the two most common histological subtypes: squamous cell carcinoma or adenocarcinoma of the esophagus. Esophageal squamous cell carcinoma arises from dysplastic squamous epithelium, usually as a result of chronic irritation. Substantial alcohol intake, especially in combination with smoking, greatly increases the risk of squamous cell carcinoma and accounts for more than 90 percent of all cases of squamous cell carcinoma of the esophagus in the developed world. Patients with recurring symptoms of reflux have an eightfold increase in the risk of developing esophageal adenocarcinoma. Ongoing gastroesophageal reflux results in the replacement of normal squamous epithelium by a columnar-lined esophagus, which is characterized by the presence of intestinal metaplasia. This so-called Barrett’s esophagus is the precursor lesion of esophageal adenocarcinoma, that develops through a metaplasia – dysplasia – carcinoma sequence

Fixed Size of Enlarged Calcified Lymph Nodes in Esophageal Adenocarcinoma despite Complete Remission

Untreated malignant lymph nodes that are calcified are rare. Publications on such calcifications are restricted to case reports. We present a case of calcified lymph nodes in a patient with adenocarcinoma of the gastroesophageal junction that seemed to be nonresponsive to induction chemotherapy, as they did not decrease in size. However, on pathological examination of the resected lymph nodes no vital tumor cells could be detected anymore. Therefore, we hypothesize that a calcified lymph node is unable to shrink, even after adequate remission on induction chemotherapy. This should be taken into account when clinical decision-making depends on the change in size of an enlarged, calcified lymph node as a measure of treatment effect

Sarcopenia/Muscle Mass is not a Prognostic Factor for Short- and Long-Term Outcome After Esophagectomy for Cancer

Background: Recent studies have suggested that sarcopenia is a prognostic risk indicator of postoperative complications and predicts survival in cancer patients. The aim of this study is to investigate whether sarcopenia is associated with postoperative short-term outcome (morbidity and mortality) and long-term survival in patients undergoing esophagectomy for cancer after neoadjuvant chemoradiotherapy. Methods: All patients who underwent neoadjuvant chemoradiotherapy followed by esophagectomy for cancer, and of whom an adequate CT scan was available, were included in the current study. The presence of sarcopenia was defined by CT imaging using cut-off values of the total cross-sectional muscle tissue measured transversely at the third lumbar level. Results: A total number of 120 patients were eligible for analysis. Almost half of the patients (N = 54, 45 %) were classified as having sarcopenia; 24 sarcopenic patients (44 %) had overweight and 5 sarcopenic patients (9 %) were obese. Overall morbidity and mortality rate did not differ significantly between sarcopenic and non-sarcopenic patients, nor did long-term overall or disease-free survival. Also sarcopenic obesity was not associated with worse outcome. Conclusion: The presence of sarcopenia was not associated with a negative short- and long-term outcome in this selected group of esophageal cancer patients after neoadjuvant chemoradiotherapy followed by esophagectomy

Comparison of the 6th and 7th editions of the UICC-AJCC TNM classification for esophageal cancer

Background. The new 7th edition of the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC) tumor, node, metastasis (TNM) staging system is the ratification of data-driven recommendations from the Worldwide Esophageal Cancer Collaboration database. Generalizability remains questionable for single institutions. The present study serves as a validation of the 7th edition of the TNM system in a prospective cohort of patients with predominantly adenocarcinomas from a single institution. Methods

Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial

Introduction Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4–8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT.Methods and analysis The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction.Ethics and dissemination The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Benzopyrene Serum Concentration After Endovenous Laser Ablation of the Great Saphenous Vein

Background: During endovenous laser ablation (EVLA) of the great saphenous vein, patients often involuntarily mention an uncomfortable “burnt” smell and taste. When applying intense heat to proteins and carbohydrates, it is inevitable that polycyclic aromatic hydrocarbons (PAHs) are formed. This group of PAH includes the human carcinogen benzo[a]pyrene (B[a]P). This study determined the serum concentration of B[a]P just before and after EVLA. Methods: A total of 20 patients were included. The B[a]P serum concentration was determined just before and directly after EVLA. Results: In 18 patients, B[a]P was determined before and after EVLA. In 2 patients, EVLA was not possible. In this study, no elevated serum concentration of B[a]P was found before and after EVLA. Conclusion: It remains to be established which heat products cause the burnt smell and taste sensation in patients during EVLA. Further research is needed to determine whether EVLA can be considered as a safe procedure

Selected stage IV rectal cancer patients managed by the watch-and-wait approach after pelvic radiotherapy: a good alternative to total mesorectal excision surgery?

Aim The aim of this study was to assess the clinical and oncological outcome of a selected group of stage IV rectal cancer patients managed by the watch-and-wait approach following a (near-)complete response of the primary rectal tumour after radiotherapy. Method Patients registered in the Dutch watch-and-wait registry since 2004 were selected when diagnosed with synchronous stage IV rectal cancer. Data on patient characteristics, treatment details, follow-up and survival were collected. The 2-year local regrowth rate, organ-preservation rate, colostomy-free rate, metastatic progression-free rate and 2- and 5-year overall survival were analysed. Results After a median follow-up period of 35 months, local regrowth was observed in 17 patients (40.5%). Nine patients underwent subsequent total mesorectal excision, resulting in a permanent colostomy in four patients. The 2-year local regrowth rate was 39.9%, the 2-year organ-preservation rate was 77.1%, the 2-year colostomy-free rate was 88.1%, and the 2-year metastatic progression-free rate was 46.7%. The 2- and 5-year overall survival rates were 92.0% and 67.5%. Conclusion The watch-and-wait approach can be considered as an alternative to total mesorectal excision in a selected group of stage IV rectal cancer patients with a (near-)complete response following pelvic radiotherapy. Despite a relatively high regrowth rate, total mesorectal excision and a permanent colostomy can be avoided in the majority of these patients

Preoperative assessment of tumor location and station-specific lymph node status in patients with adenocarcinoma of the gastroesophageal junction

Contains fulltext : 125789.pdf (publisher's version ) (Closed access)In esophageal cancer patients preoperative staging will determine the type of surgical procedure and use of neoadjuvant therapy. Tumor location and lymph node status play a pivotal role in this tailored strategy. The aim of the present study was to prospectively evaluate the accuracy of preoperative assessment of tumor location according to the Siewert classification and lymph node status per station with endoscopy/endoscopic ultrasound (EUS) and computed tomography (CT).In 50 esophagectomy patients with adenocarcinoma of the gastroesophageal junction (GEJ), tumor location according to Siewert and N-stage per nodal station as determined preoperatively by endoscopy/EUS and CT were compared with the histopathologic findings in the resection specimen.Overall accuracy in predicting tumor location according to the Siewert classification was 70 \% for endoscopy/EUS and 72 \% for CT. Preoperative data could not be compared with the pathologic assessment in 11 patients (22 \%), as large tumors obscured the landmark of the gastric folds. The overall accuracy for predicting the N-stage in 250 lymph node stations was 66 \% for EUS and 68 \% for CT. The accuracy was good for those stations located high in the thorax, but poor for celiac trunk nodes.Given the frequent discrepancy between the endoscopic and pathologic location of the GEJ and the common problem of advanced tumors obscuring the landmarks used in the assessment of the Siewert classification, its usefulness is limited. The overall accuracy for EUS and CT in predicting the N-stage per station was moderate

Inter- and intraobserver variation in the histopathological evaluation of early oesophageal adenocarcinoma

Aims According to the classification established by the Japanese Society for Oesophageal Disease, early oesophageal cancer can be subdivided into six successive layers of the mucosa or submucosa, which influences the treatment strategy and prognosis of the individual patient. However, the reproducibility of this classification in terms of inter-and intraobserver variability is unclear. Methods Histological slides from 105 surgical resection specimens of patients who had undergone oesophagectomy for early oesophageal adenocarcinoma were reviewed independently by three gastrointestinal pathologists, and were classified according to the Japanese criteria (m1/m2/m3/sm1/sm2/sm3 tumours). Inter-and intraobserver variation was determined by k-statistics. Results The interobserver reproducibility was good between pathologist 1 and 2 (kappa=0.61, 95% CI 0.55 to 0.67), and moderate between pathologist 1 and 3 (kappa-0.51, 95% CI 0.45 to 0.57) and between pathologist 2 and 3 (kappa=0.50, 95% CI 0.38 to 0.61). The intraobserver agreement as assessed by the expert pathologist was good (kappa=0.76), with a 95% CI that was interpreted as good to very good (0.67 to 0.85). Most agreement was achieved at the lower (m1) and upper site (sm2, sm3) of the spectrum, whereas the m2 tumours reflected the most discrepant stage. The majority of the observed discrepancy included the variation in one substage only. Conclusions The reproducibility of the Japanese classification is good in terms of inter- and intraobserver variability when grading early oesophageal adenocarcinoma on surgical resection specimens. The present data confirm that dedicated gastrointestinal pathologists with broad experience are preferred when grading the resection specimens of patients with early oesophageal adenocarcinom