Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: Long-term results of a randomized controlled trial

Background: This is a randomized, controlled trial of preoperative chemotherapy in patients undergoing surgery for oesophageal squamous cell carcinoma (OSCC). Patients were allocated to chemotherapy, consisting of 2-4 cycles of cisplatin and etoposide, followed by surgery (CS group) or surgery alone (S group). Initial results reported only in abstract form in 1997, demonstrated an advantage for overall survival in the CS group. The results of this trial have been updated and discussed in the timeframe in which this study was performed.Methods: This trial recruited 169 patients with OSCC, 85 patients assigned to preoperative chemotherapy and 84 patients underwent immediate surgery. The primary study endpoint was overall survival (OS), secondary endpoints were disease free survival (DFS) and pattern of failure. Survival has been determined from Kaplan-Meier curves and treatment comparisons made with the log-rank test.Results: There were 148 deaths, 71 in the CS and 77 in the S group. Median OS time was 16 months in the CS group compared with 12 months in the S group; 2-year survival rates were 42% and 30%; and 5-year survival rates were 26% and 17%, respectively. Intention to treat analysis showed a significant overall survival benefit for patients in the CS group (P = 0.03, by the log-rank test; hazard ratio [HR] 0.71; 95%CI 0.51-0.98). DFS (from landmark time of 6 months after date of randomisation) was also better in the CS-group than in the S group (P = 0.02, by the log-rank test; HR 0.72; 95%CI 0.52-1.0). No difference in failure pattern was observed between both treatment arms.Conclusions: Preoperative chemotherapy with a combination of etoposide and cisplatin significantly improved overall survival in patients with OSCC

Individual risk calculator to predict lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma:a multicenter cohort study

Background Lymph node metastasis (LNM) is possible after endoscopic resection of early esophageal adenocarcinoma (EAC). This study aimed to develop and internally validate a prediction model that estimates the individual risk of metastases in patients with pT1b EAC. Methods A nationwide, retrospective, multicenter cohort study was conducted in patients with pT1b EAC treated with endoscopic resection and/or surgery between 1989 and 2016. The primary end point was presence of LNM in surgical resection specimens or detection of metastases during follow-up. All resection specimens were histologically reassessed by specialist gastrointestinal pathologists. Subdistribution hazard regression analysis was used to develop the prediction model. The discriminative ability of this model was assessed using the c-statistic. Results 248 patients with pT1b EAC were included. Metastases were seen in 78 patients, and the 5-year cumulative incidence was 30.9 % (95 % confidence interval [CI] 25.1 %-36.8 %). The risk of metastases increased with submucosal invasion depth (subdistribution hazard ratio [SHR] 1.08, 95 %CI 1.02-1.14, for every increase of 500 μm), lymphovascular invasion (SHR 2.95, 95 %CI 1.95-4.45), and for larger tumors (SHR 1.23, 95 %CI 1.10-1.37, for every increase of 10 mm). The model demonstrated good discriminative ability (c-statistic 0.81, 95 %CI 0.75-0.86). Conclusions A third of patients with pT1b EAC experienced metastases within 5 years. The probability of developing post-resection metastases was estimated with a personalized predicted risk score incorporating tumor invasion depth, tumor size, and lymphovascular invasion. This model requires external validation before implementation into clinical practice

Does Giardia lamblia Cause Villous Atrophy in Children?: A Retrospective Cohort Study of the Histological Abnormalities in Giardiasis

Objective: To determine the prevalence and type of histological abnormalities in duodenal mucosa associated with Giardia lamblia in children who undergo esophagogastroduodenoscopy. Materials and Methods: Duodenal biopsies containing G lamblia were retrieved from all paediatric patients who had undergone endoscopy in our centre in the last 20 years. These biopsies were scored for histological abnormalities by a single pathologist using a semiquantative scale and staged according to the Marsh criteria. In those with a Marsh stage above 0, the presence of coeliac disease was investigated. Results: After excluding all patients with concomitant coeliac disease, 4 out of 32 (13%) patients had a biopsy showing crypt hyperplasia and 1 out of 32 (3%) had partial villous atrophy. No intraepithelial lymphocytosis was found. In our cohort, 2 patients with giardiasis and mild histological abnormalities were diagnosed with coeliac disease only after a repeated endoscopy and serology were performed; in 1 of them after a delay of 5 years. Other histological abnormalities frequently observed were increased eosinophilic infiltration of the lamina propria (35%) and lymph follicle formation (35%). Infiltration of neutrophilic and eosinophilic granulocytes in the epithelial layer was observed less frequently (16% and 9%, respectively). Conclusions: Villous atrophy, intraepithelial lymphocytosis and/or crypt hyperplasia are rare in children with giardiasis who undergo esophagogastroduodenoscopy. Therefore, other causes, particularly coeliac disease, should always be suspected. This study, however, suggests that giardiasis can cause chronic mucosal inflammation, often of an eosinophilic nature, in these children. JPGN 49: 304-308, 200

Is gluten challenge really necessary for the diagnosis of coeliac disease in children younger than age 2 years?

OBJECTIVE: In the diagnosis of coeliac disease (CD), gluten challenge is recommended for children under the age of 2 years at initial biopsy. The aim of the study was to investigate the diagnostic yield of gluten challenge in this group of children. PATIENTS AND METHODS: We included children aged 2 years or younger who were analysed for possible CD and who had villous atrophy at initial small bowel biopsy in the period 1993-2004. We subsequently identified all patients who underwent a complete gluten challenge. RESULTS: We identified 333 children with possible CD. In 100 children (30%), a gluten challenge was performed, with the diagnosis being confirmed in 97. Retrospectively, in 2 of the 3 children without mucosal relapse, data available before gluten challenge did not justify the initial diagnosis of CD. In the third patient, transient gluten intolerance could not be excluded. At first biopsy, the 2 children without mucosal relapse had negative serological parameters, whereas the third patient had IgA antigliadin antibodies, but no IgA anti-endomysium antibodies (EMA). Indeed, all of the patients with EMA at diagnosis had a relapse at gluten challenge. CONCLUSIONS: Routine gluten challenge in children younger than 2 years at initial diagnosis of CD has an extremely low diagnostic yield. We suggest that routine gluten challenge in this group of patients is not necessary when patients have villous atrophy in combination with EMA. Therefore, a revision of the current diagnostic criteria has to be considere

Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT trial)

For esophageal cancer patients, radical esophagolymphadenectomy is the cornerstone of multimodality treatment with curative intent. Transthoracic esophagectomy is the preferred surgical approach worldwide allowing for en-bloc resection of the tumor with the surrounding lymph nodes. However, the percentage of cardiopulmonary complications associated with the transthoracic approach is high (50 to 70%).Recent studies have shown that robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RATE) is at least equivalent to the open transthoracic approach for esophageal cancer in terms of short-term oncological outcomes. RATE was accompanied with reduced blood loss, shorter ICU stay and improved lymph node retrieval compared with open esophagectomy, and the pulmonary complication rate, hospital stay and perioperative mortality were comparable. The objective is to evaluate the efficacy, risks, quality of life and cost-effectiveness of RATE as an alternative to open transthoracic esophagectomy for treatment of esophageal cancer. This is an investigator-initiated and investigator-driven monocenter randomized controlled parallel-group, superiority trial. All adult patients (age ≥ 18 and ≤ 80 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal carcinoma of the intrathoracic esophagus and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 112) with resectable esophageal cancer are randomized in the outpatient department to either RATE (n = 56) or open three-stage transthoracic esophageal resection (n = 56). The primary outcome of this study is the percentage of overall complications (grade 2 and higher) as stated by the modified Clavien-Dindo classification of surgical complications. This is the first randomized controlled trial designed to compare RATE with open transthoracic esophagectomy as surgical treatment for resectable esophageal cancer. If our hypothesis is proven correct, RATE will result in a lower percentage of postoperative complications, lower blood loss, and shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with open transthoracic esophagectomy. The study started in January 2012. Follow-up will be 5 years. Short-term results will be analyzed and published after discharge of the last randomized patient. Dutch trial register: NTR3291 ClinicalTrial.gov: NCT0154479