Perioperative and Oncological Outcome of Laparoscopic Resection of Gastrointestinal Stromal Tumour (GIST) of the Stomach

Background. Surgery remains the only curative treatment for gastrointestinal stromal tumour (GIST). Resection needs to ensure tumour-free margins while lymphadenectomy is not required. Thus, partial gastric resection is the treatment of choice for small gastric GISTs. Evidence on whether performing resection laparoscopically compromises outcome is limited. Methods. We compiled patients undergoing laparoscopic resection of suspected gastric GIST between 2003 and 2007. Follow-up was performed to obtain information on tumour recurrence. Results. Laparoscopic resection with free margins was performed in 21/22 patients. Histology confirmed GIST in 17 cases, 4 tumours were benign neoplasms. Median operation time and postoperative stay for GIST patients were 130 (range 80–201) mins and 7 (range 5–95) days. Two patients experienced stapler line leakage necessitating surgical revision. After median follow-up of 18 (range 1–53) months, no recurrence occurred. Conclusions. Laparoscopic resection of gastric GISTs yields good perioperative outcomes. Oncologic outcome needs to be assessed with longer follow-up. For posterior lesions, special precaution is needed. Laparoscopic resection could become standard for circumscribed gastric GISTs if necessary precautions for oncological procedures are observed

Laparoscopic Heller Myotomy Versus Endoscopic Balloon Dilatation for the Treatment of Achalasia A Network Meta-Analysis

Objective: Comparison of short-and long-term effects after laparoscopic Heller myotomy (LHM) and endoscopic balloon dilation (EBD) considering the need for retreatment. Background: Previously published studies have indicated that LHM is the most effective treatment for Achalasia. In contrast to that a recent randomized trial found EBD equivalent to LHM 2 years after initial treatment. Methods: A search in Medline, PubMed, and Cochrane Central Register of Controlled Trials was conducted for prospective studies on interventional achalasia therapy with predefined exclusion criteria. Data on success rates after the initial and repeated treatment were extracted. An adjusted network meta-analysis and meta-regression analysis was used, combined with a headto-head comparison, for follow-up at 12, 24, and 60 months. Results: Sixteen studies including results of 590 LHM and EBD patients were identified. Odds ratio (OR) was 2.20 at 12 months (95% confidence interval: 1.18-4.09; P = 0.01); 5.06 at 24 months (2.61-9.80; P < 0.00001) and 29.83 at 60 months (3.96-224.68; P = 0.001). LHM was also significantly superior for all time points when therapy included re-treatments , and 17.90 (2.17-147.98); P ≤ 0.01 for all comparisons) Complication rates were not significantly different. Meta-regression analysis showed that amount of dilations had a significant impact on treatment effects (P = 0.009). Every dilation (up to 3) improved treatment effect by 11.9% (2.8%-21.8%). Conclusions: In this network meta-analysis, LHM demonstrated superior short-and long-term efficacy and should be considered first-line treatment of esophageal achalasia. Keywords: achalasia, economic cost, endoscopy, esophagus, health, idiopathic achalasia, laparoscopic surgery, meta-analysis, motility disorders, network meta-analysis, review, surgery (Ann Surg 2013;258:943-952 A chalasia is a rare esophageal motility disorder caused by degeneration of the myenteric plexus, resulting in esophageal dysmotility and incomplete lower esophageal sphincter relaxation. The disease is likely caused by a virus-induced autoimmune response, but this is still debated. 1 The incidence in the Western world is 1/100 000. 2-4 Treatment can be pharmacological, endoscopic, or surgical. Pharmacological treatment is only marginally effective and is reserved for patients with mild symptoms or who refuse other treatments. 7-9 Several studies and a large meta-analysis have indicated that laparoscopic Heller myotomy (LHM) is the most effective treatment for achalasia. 3,4,10 However, a recent large prospective randomized controlled trial (RCT) comparing EBD and LHM has challenged this view. 11 This study found similar success rates for EBD and LHM 2 years after initial treatment. However, the number of EBD interventions per patient was notably higher than other studies. 3,11 The purpose of this meta-analysis is to determine which treatment is most effective at relieving symptoms and to further clarify the impact of retreatments for patients with achalasia. METHODS This meta-analysis was registered in the international register of systematic reviews (PROSPERO) (CRD42012002071). 12 Search Strategy and Trial Selection A prospective search of Medline, PubMed, and Cochrane Central Register of Controlled Trials was performed to identify relevant publications. The search keyword was "Esophageal Achalasia." Subsequently, the search was limited by the terms "Human," "Clinical Trial," and publication language "English." Publications from 1975 through October 2011 were considered for review To obtain indirect evidence by adjusted network meta-analysis, relative evidence is needed (LHM vs X; EBD vs X). Therefore, success rates were compared with those of either EBTI or open Heller myotomy (OHM). Direct evidence was achieved from head-to-hea

Brain metastasis and survival outcomes after first-line therapy in metastatic melanoma: a multicenter DeCOG study on 1704 patients from the prospective skin cancer registry ADOREG

Background Despite the availability of effective systemic therapies, a significant number of advanced melanoma patients develops brain metastases. This study investigated differences in incidence and time to diagnosis of brain metastasis and survival outcomes dependent on the type of first-line therapy.Methods Patients with metastatic, non-resectable melanoma (AJCCv8 stage IIIC–V) without brain metastasis at start of first-line therapy (1L-therapy) were identified from the prospective multicenter real-world skin cancer registry ADOREG. Study endpoints were incidence of brain metastasis, brain metastasis-free survival (BMFS), progression-free survival (PFS), and overall survival (OS).Results Of 1704 patients, 916 were BRAF wild-type (BRAFwt) and 788 were BRAF V600 mutant (BRAFmut). Median follow-up time after start of 1L-therapy was 40.4 months. BRAFwt patients received 1L-therapy with immune checkpoint inhibitors (ICI) against CTLA-4+PD-1 (n=281) or PD-1 (n=544). In BRAFmut patients, 1L-therapy was ICI in 415 patients (CTLA-4+PD-1, n=108; PD-1, n=264), and BRAF+MEK targeted therapy (TT) in 373 patients. After 24 months, 1L-therapy with BRAF+MEK resulted in a higher incidence of brain metastasis compared with PD-1±CTLA-4 (BRAF+MEK, 30.3%; CTLA-4+PD-1, 22.2%; PD-1, 14.0%). In multivariate analysis, BRAFmut patients developed brain metastases earlier on 1L-therapy with BRAF+MEK than with PD-1±CTLA-4 (CTLA-4+PD-1: HR 0.560, 95% CI 0.332 to 0.945, p=0.030; PD-1: HR 0.575, 95% CI 0.372 to 0.888, p=0.013). Type of 1L-therapy, tumor stage, and age were independent prognostic factors for BMFS in BRAFmut patients. In BRAFwt patients, tumor stage was independently associated with longer BMFS; ECOG Performance status (ECOG-PS), lactate dehydrogenase (LDH), and tumor stage with OS. CTLA-4+PD-1 did not result in better BMFS, PFS, or OS than PD-1 in BRAFwt patients. For BRAFmut patients, multivariate Cox regression revealed ECOG-PS, type of 1L-therapy, tumor stage, and LDH as independent prognostic factors for PFS and OS. 1L-therapy with CTLA-4+PD-1 led to longer OS than PD-1 (HR 1.97, 95% CI 1.122 to 3.455, p=0.018) or BRAF+MEK (HR 2.41, 95% CI 1.432 to 4.054, p=0.001), without PD-1 being superior to BRAF+MEK.Conclusions In BRAFmut patients 1L-therapy with PD-1±CTLA-4 ICI resulted in a delayed and less frequent development of brain metastasis compared with BRAF+MEK TT. 1L-therapy with CTLA-4+PD-1 showed superior OS compared with PD-1 and BRAF+MEK. In BRAFwt patients, no differences in brain metastasis and survival outcomes were detected for CTLA-4+PD-1 compared with PD-1

Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>For patients with locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor <it>(VEGF-R</it>) and Transketolase-like-1 (<it>TKTL1</it>) are related to hypoxic conditions in tumours. In search for potential prognostic molecular markers we investigated the expression of <it>VEGFR-1</it>, <it>VEGFR-2 </it>and <it>TKTL1 </it>in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab.</p> <p>Methods</p> <p>Tumour and corresponding normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median age: 61 years) with LARC treated in phase-I and II trials with neoadjuvant chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with radiotherapy) were analysed by quantitative PCR.</p> <p>Results</p> <p>Significantly higher expression of <it>VEGFR-1/2 </it>was found in tumour tissue in pre-treatment biopsies as well as in resected specimen after neoadjuvant chemoradiotherapy compared to corresponding normal tissue. High <it>TKTL1 </it>expression significantly correlated with disease free survival. None of the markers had influence on early response parameters such as tumour regression grading. There was no correlation of gene expression between the investigated markers.</p> <p>Conclusion</p> <p>High <it>TKTL-1 </it>expression correlates with poor prognosis in terms of 3 year disease-free survival in patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may therefore serve as a molecular prognostic marker which should be further evaluated in randomised clinical trials.</p