Christianne J. Buskens

Outcome of surgical treatment for early adenocarcinoma of the esophagus or gastro-esophageal junction.

Adenocarcinoma of the esophagus, or GEJ, has a poor prognosis. Early lesions [i.e. high grade dysplasia (HGD) or T1-carcinoma] are potentially curable. Local endoscopic therapies are promising treatment options for superficial lesions; however, for deeper lesions, surgical resection is considered to be the treatment of choice. To contribute to therapeutic decision-making, we retrospectively analysed the outcome of transhiatal esophagectomy in 120 patients with pathologically proven HGD (n=13) or T1-adenocarcinoma (n=107) of the distal esophagus or gastro-esophageal junction (GEJ). Tumors were subdivided into six different depths of invasion (‘T1-mucosal’ m1-m3, ‘T1-submucosal’ sm1-sm3), and the frequency of lymphatic dissemination and time to locoregional and/or distant recurrence were analysed. Only one of the 79 T1m1-3/sm1 tumors (1%) showed lymph node metastases as compared with 18 out of 41 T1sm2-3 tumors (44%). There was a significant difference in recurrence-free period between T1m1-m3/sm1 versus T1sm2-sm3 tumor patients (P log rank <0.0001), with 5-year recurrence-free percentages of 97% and 57%, respectively. In multivariate analysis including age, gender, tumor differentiation grade, N-stage and depth of invasion, only N-stage was an independent prognostic factor for recurrence-free period (hazard rate=5.9, 95% CI 1.7–20.7). However, if N-stage was excluded from analysis, only depth of invasion (T1sm2-3 versus T1m1-m3/sm1) was an independent prognostic factor for recurrence-free period (hazard rate=7.5, 95% CI 2.0–27.7). These data indicate that T1m1-m3/sm1 adenocarcinomas of esophagus or GEJ show a very low risk of lymphatic dissemination and are therefore eligible for local endoscopic therapy. After transhiatal surgical resection, almost half of the patients with T1sm2-sm3 lesions develop recurrent disease within 5 years, and therefore need additional therapy to improve survival.

Prediction of appropriateness of local endoscopic treatment for high-grade dysplasia and early adenocarcinoma by EUS and histopathologic features

BACKGROUND Endoscopic techniques are being developed for the local treatment of early stage esophageal cancer. However, such therapy is not appropriate for patients with lymph node metastasis. The aim of this study was to analyze the histopathologic features of high-grade dysplasia and early stage adenocarcinoma and to relate these to lymph node involvement. METHODS Pathology reports were reviewed for all 367 patients who underwent subtotal esophagectomy for high-grade dysplasia or adenocarcinoma of the esophagus or the gastroesophageal junction between January 1993 and December 2001. Patients with histopathologically confirmed high-grade dysplasia or T1 carcinoma were included (n = 77). Pre-operative EUS results were assessed. All lesions were histopathologically subdivided in 6 different stages (mucosal 1-3 and submucosal 1-3). RESULTS EUS staged 61 patients as N0. EUS correctly predicted the absence of positive lymph nodes in 57 (93%) of these patients. Histopathologically, m1, m2, m3, and sm1 cancers never had lymph node metastases, whereas 3 of 13 sm2 tumors (23%) and 9 of 13 sm3 tumors (69%) had lymph node involvement. Lymphangio invasion was present exclusively in sm2 and sm3 cancers. Factors that predicted the presence of lymph node metastasis were the following: tumor diameter greater than 3 cm, infiltration of malignancy beyond sm1, poor differentiation grade, and lymphangio invasion, although only infiltration beyond sm1 remained significant in the definitive multivariate analysis. CONCLUSIONS EUS and the histopathologic features of high-grade dysplasia and early stage adenocarcinoma of the esophagus or the gastroesophageal junction can predict the presence of lymph node involvement. These data can be used to identify patients for whom local endoscopic treatment may be appropriate.

Interleukin-12 and -23 Control Plasticity of CD127+ Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria

Human group 1 ILCs consist of at least three phenotypically distinct subsets, including NK cells, CD127(+) ILC1, and intraepithelial CD103(+) ILC1. In inflamed intestinal tissues from Crohns disease patients, numbers of CD127(+) ILC1 increased at the cost of ILC3. Here we found that differentiation of ILC3 to CD127(+) ILC1 is reversible in vitro and in vivo. CD127(+) ILC1 differentiated to ILC3 in the presence of interleukin-2 (IL-2), IL-23, and IL-1β dependent on the transcription factor RORγt, and this process was enhanced in the presence of retinoic acid. Furthermore, we observed in resection specimen from Crohns disease patients a higher proportion of CD14(+) dendritic cells (DC), which in vitro promoted polarization from ILC3 to CD127(+) ILC1. In contrast, CD14(-) DCs promoted differentiation from CD127(+) ILC1 toward ILC3. These observations suggest that environmental cues determine the composition, function, and phenotype of CD127(+) ILC1 and ILC3 in the gut.

Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer

Neoadjuvant chemoradiotherapy (CRT) has been proven to increase local control in rectal cancer, but the optimal interval between CRT and surgery is still unclear. The purpose of this study was to analyse the influence of variations in clinical practice regarding timing of surgery on pathological response at a population level.

Cyclooxygenase-2 and gastric carcinogenesis

Epidemiological studies have shown that the use of nonsteroid anti‐inflammatory drugs (NSAIDs) is associated with reduced risk of gastric cancer. The best‐known target of NSAIDs is the cyclooxygenase (Cox) enzyme. Two Cox genes have been cloned, of which Cox‐2 has been connected with gastric carcinogenesis. Expression of Cox‐2 is elevated in gastric adenocarcinomas, which correlates with several clinicopathological parameters, including depth of invasion and lymph node metastasis. This suggests that Cox‐2–derived prostanoids promote aggressive behavior of adenocarcinomas of the stomach. Cox‐2 expression is especially prominent in intestinal‐type gastric carcinoma and it is already present in dysplastic precursor lesions of this disease, which suggests that Cox‐2 contributes to gastric carcinogenesis already at the preinvasive stage. Our most recent data show that Cox‐2 is expressed in gastric adenomas of trefoil factor 1 deficient mice. Treatment of these mice with a Cox‐2 selective inhibitor, celecoxib, reduced the size of the adenomas. Taken together these data support efforts to initiate clinical studies to investigate the effect of Cox‐2 inhibitors as chemotherapeutic agents and as adjuvant treatment modalities against gastric neoplasias.

3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 2: Surgical Management and Special Situations

This paper is the second in a series of two publications relating to the European Crohns and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohns disease [CD] and concerns the surgical management of CD as well as special situations including management of perianal CD and extraintestinal manifestations. Diagnostic approaches and medical management of CD of this ECCO Consensus are covered in the first paper [Gomollon et al JCC 2016].

Benign tracheo-neo-esophageal fistulas after subtotal esophagectomy

BACKGROUND Benign tracheo-neo-esophageal fistulas after esophagectomy are rare and treatment can be challenging. They can result from perioperative tracheal injury or various postoperative complications. METHODS Charts of 6 patients with a benign tracheoneo-esophageal fistula after subtotal esophagectomy treated in this institution between July 1993 and August 1999 were analyzed. RESULTS Three men and 3 women (median age 61 years) developed a fistula after subtotal esophagectomy. Symptoms varied from mild swallowing difficulties to aspiration pneumonia and mediastinitis. Two patients with mild symptoms were treated conservatively. In 1 patient a long fistula was partly excised through the neck. In 3 patients the gastric tube was excluded or excised, with surgical closure of the tracheal defect. The alimentary tract was reconstructed by colonic interposition. There were no major complications. After a median follow-up of 1.6 years, all fistulas were closed. All patients were capable of sufficient oral intake. CONCLUSIONS A benign tracheo-neo-esophageal fistula after esophagectomy is a rare, but serious complication. Site and size of the fistula, together with the severity of symptoms, should dictate management.

Perineal wound healing after abdominoperineal resection for rectal cancer: a systematic review and meta-analysis.

BACKGROUND: Impaired perineal wound healing has become a significant clinical problem after abdominoperineal resection for rectal cancer. The increased use of neoadjuvant radiotherapy and wider excisions might have contributed to this problem. OBJECTIVE: The primary aim of this systematic review with meta-analysis was to determine the impact of radiotherapy and an extralevator approach on perineal wound healing after abdominoperineal resection for rectal cancer. DATA SOURCES: In March 2014, electronic databases were searched. STUDY SELECTION AND INTERVENTIONS: Studies describing any outcome measure on perineal wound healing after abdominoperineal resection for rectal cancer were included. MAIN OUTCOME MEASURES: The primary end point was overall perineal wound problems within 30 days after conventional or extralevator abdominoperineal resection with or without neoadjuvant radiotherapy. Secondary end points were primary wound healing, perineal hernia rate, and the effect of biological mesh closure on perineal wound problems. RESULTS: A total of 32 studies were included. The pooled percentage of perineal wound problems after primary perineal wound closure in patients who did not undergo neoadjuvant radiotherapy was 15.3% (95% CI, 12.1–19.2) after conventional abdominoperineal resection and 14.8% (95% CI, 9.5–22.4) after extralevator abdominoperineal resection. After neoadjuvant radiotherapy, perineal wound problems occurred in 30.2% (95% CI, 19.2–44.0) after conventional abdominoperineal resection and in 37.6% (95% CI, 18.6–61.4) after extralevator abdominoperineal resection. Radiotherapy significantly increased perineal wound problems after abdominoperineal resection (OR, 2.22; 95% CI, 1.45–3.40; p < 0.001). After biological mesh closure of the pelvic floor following extralevator abdominoperineal resection with neoadjuvant radiotherapy, the percentage of perineal wound problems was 7.3% (95% CI, 1.5–29.3). LIMITATIONS: Heterogeneity was high for some analyses. CONCLUSION: Neoadjuvant radiotherapy significantly increases perineal wound problems after abdominoperineal resection for rectal cancer, whereas the extralevator approach seems not to be of significant importance.

Systematic review and meta-analysis of laparoscopic versus open colectomy with end ileostomy for non-toxic colitis.

This review compared short‐term outcomes after laparoscopic versus open subtotal colectomy for acute, colitis medically refractory.

Comparison of cyclooxygenase 2 expression in adenocarcinomas of the gastric cardia and distal oesophagus.

Background: Adenocarcinomas of the gastric cardia and distal oesophagus are at present often considered as one clinical entity because of their comparable increasing incidence, prognosis, and optimal treatment options. However, it is still a matter of debate whether these malignancies have the same pathogenesis and genotype. Aims: The aim of this study was to analyse expression of cyclooxygenase 2 (COX-2) in cardia carcinomas, and correlate this expression with clinicopathological parameters and survival. The results were compared with the prognostic value of COX-2 found for Barrett carcinomas. Methods: Tumour sections of 134 consecutive patients undergoing potentially curative surgery for an adenocarcinoma of the gastric cardia and substantially invading the distal oesophagus were immunohistochemically stained using a COX-2 monoclonal antibody. Specimens were blindly scored based on intensity and extent of COX-2 immunopositivity. Results: COX-2 expression was negative to weak in 59% (“COX-2 low”) and moderate to strong in 41% (“COX-2 high”) of tumours. This was significantly lower than in Barrett carcinomas (p<0.0001). COX-2 expression was not correlated with any clinicopathological parameter. A correlation between elevated COX-2 expression and reduced survival, as described for Barrett carcinomas, was not identified for cardiac carcinomas. Conclusions: There is a difference in COX-2 expression with respect to intensity and prognostic significance between adenocarcinomas of the gastric cardia and distal oesophagus. This suggests a different pathogenesis and different genetic constitution of these two cancers. Based on these findings, the role of selective COX-2 inhibitors in the treatment of adenocarcinomas of the gastric cardia is less promising than in Barrett carcinomas.