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Pancreatic cancer is one of the most lethal gastrointestinal tumor entities. Surgery is the only chance for cure; however, only a minority of patients can be offered this option. Due to the anatomic location of the gland, tumor-related problems and complications affecting the surrounding structures are common, leading to biliary and gastric outlet obstruction as well as portal vein thrombosis. This review article summarizes the management of pancreatic cancer-related problems from a surgical point of view. We further describe surgical treatment options in unresectable, metastasized and recurring pancreatic cancer, highlighting potential resection of oligometastatic disease in selected settings.

Background The purpose of this study was to investigate clinical features, prognostic factors, and overall survival (OS) in surgical patients with gastric remnant cancer (GRC). Methods A retrospective analysis of patients with gastrectomy for pT1–4 gastric cancer between October 1972 and February 2014 at our institution was performed. Clinical characteristics were compared between patients with GRC and those with primary gastric cancer (PGC). Multivariable Cox regression analysis was performed to determine the prognostic factors for OS in patients with GRC. A propensity score-matched cohort was used to investigate OS between the GRC and PGC groups. Results Of a baseline cohort of 1440 patients, 95 patients with GRC were identified. Patients with GRC underwent more multivisceral resections (p p = 0.018); however, R0 resection rates were not significantly different (p = 0.211). The postoperative overall (p = 0.032) and major surgical (p = 0.021) complication rates and the 30-day (p = 0.003) and in-hospital (p = 0.008) mortality rates were higher in patients with GRC. In multivariable analysis, the only prognostic factors for worse OS in GRC were higher tumor stage (p p p = 0.772). Conclusions GRC required more invasive surgery than PGC; however, the feasibility of R0 resection was similar. The prognostic factors of GRC were similar to those of PGC, and OS was not significantly different between both groups. Patients with GRC benefit from extensive surgery when performed with low morbidity and mortality.

(1) Background: Numerous dissection instruments are available for liver resection. So far, there has been no evidence in favor of a specific dissection device effecting a reduction in postoperative mortality and morbidity or a reduction in intraoperative blood loss. The aim of the study was to evaluate the safety of liver resection with the 1318 nm surgical laser. (2) Methods: 151 consecutive patients who underwent liver resection using the 1318 nm surgical laser (n = 119) or conventional dissection methods (n = 32) were evaluated retrospectively. As primary outcome, postoperative complications were assessed using the Clavien–Dindo classification. Secondary outcomes were postoperative mortality, reoperations and reinterventions, intraoperative blood loss, the need for vascular control using the Pringle maneuver and oncological safety assessed through histopathological evaluation of resection margins. (3) Results: For liver resections using the 1318 nm surgical laser, the postoperative morbidity (41.2% vs. 59.4%, p = 0.066), mortality (1.7% vs. 3.1%, p = 0.513) and the reoperation rate (2.5% vs. 3.1%, p = 1.000) were not significantly different from conventional liver resections. In the laser group, a lower reintervention rate (9.2% vs. 21.9%, p = 0.050) was observed. The oncological safety demonstrated by a tumor-free resection margin was similar after laser and conventional resection (93.2% vs. 89.3%, p = 0.256). The median intraoperative blood loss was significantly lower in the laser group (300 mL vs. 500 mL, p = 0.005) and there was a significantly lower need for a Pringle maneuver (3.4% vs. 15.6%, p = 0.021). (4) Conclusions: Liver resections using the 1318 nm surgical laser can be routinely performed with a favorable risk profile. Compared to alternative resection methods, they are associated with low blood loss, appear adequate from an oncological point of view, and are not associated with increased mortality and morbidity.

Preoperative devascularization might improve local control and thus the outcome of patients with soft tissue sarcoma (STS). The multikinase inhibitor pazopanib has antiangiogenic effects and is approved for treating metastatic STS. We conducted a trial of preoperative pazopanib therapy in high-risk STS. This single-arm, phase II trial included patients with resectable, non-metastatic, treatment-naive, high-risk STS. Patients received pazopanib 800 mg daily while waiting for surgery (21-day ‘window of opportunity’). The primary endpoint was metabolic response rate (MRR; proportion of patients with ≥ 50% reduction of mean standardized uptake value [SUVmean] in post- vs. pretreatment fluorodeoxyglucose–positron emission tomography/computed tomography [FDG-PET-CT]). Planned sample size was 35 patients (type I error, 5%; type II error, 20%). A translational substudy explored associations between response and concentration of circulating angiogenic factors. Futility analysis was performed after 21 patients (11 female, mean age 67 years; liposarcoma n = 15); 17/21 patients were evaluable for the primary endpoint. The MRR was 1/17 (5.9%, 95% confidence interval

Simple Summary Tracheoesophageal fistulae (TEF) after oncologic resections represent a therapeutic challenge. Reconstructive options vary from the upper to the lower airways and include the complete therapeutic armamentarium from pedicled flaps to chimeric free flaps. Derived from the experience of 18 oncologic patients with TEF, we present a therapeutic algorithm that may guide future treatment strategies and shows that an interdisciplinary approach leads to satisfying success rates. However, disease-specific morbidity has to be anticipated. Abstract Background: Tracheoesophageal fistulae (TEF) after oncologic resections and multimodal treatment are life-threatening and surgically challenging. Radiation and prior procedures hamper wound healing and lead to high complication rates. We present an interdisciplinary algorithm for the treatment of TEF derived from the therapy of consecutive patients. Patients and methods: 18 patients (3 females, 15 males) treated for TEF from January 2015 to July 2017 were included. Two patients were treated palliatively, whereas reconstructions were attempted in 16 cases undergoing 24 procedures. Discontinuity resection and secondary gastric pull-up were performed in two patients. Pedicled reconstructions were pectoralis major (n = 2), sternocleidomastoid muscle (n = 2), latissimus dorsi (n = 1) or intercostal muscle (ICM, n = 7) flaps. Free flaps were anterolateral thigh (ALT, n = 4), combined anterolateral thigh/anteromedial thigh (ALT/AMT, n = 1), jejunum (n = 3) or combined ALT–jejunum flaps (n = 2). Results: Regarding all 18 patients, 11 of 16 reconstructive attempts were primarily successful (61%), whereas long-term success after multiple procedures was possible in 83% (n = 15). The 30-day survival was 89%. Derived from the experience, patients were divided into three subgroups (extrathoracic, cervicothoracic, intrathroracic TEF) and a treatment algorithm was developed. Primary reconstructions for extra- and cervicothoracic TEF were pedicled flaps, whereas free flaps were used in recurrent or persistent cases. Pedicled ICM flaps were mostly used for intrathoracic TEF. Conclusion: TEF after multimodal tumor treatment require concerted interdisciplinary efforts for successful reconstruction. We describe a differentiated reconstructive approach including multiple reconstructive techniques from pedicled to chimeric ALT/jejunum flaps. Hereby, successful reconstructions are mostly possible. However, disease and patient-specific morbidity has to be anticipated and requires further interdisciplinary management.

In the framework of the German Interdisciplinary Sarcoma Group GISG-04/NOPASS trial, we evaluated soft tissue sarcoma samples taken before and after neoadjuvant pazopanib therapy using histopathology and next generation sequencing (NGS) to find potential predictive biomarkers. We also aimed to improve the genetically based sarcoma classification and to elucidate additional potentially druggable mutations. In total, 30 tumor samples from 18 patients consisting of 12 pre-therapeutic biopsies and 18 resection specimens following neoadjuvant pazopanib therapy were available for analyses. NGS was performed with the Oncomine Focus Assay (Ion Torrent) covering 0.03 Mb of DNA and enabled the detection of genetic variants in 52 cancer-relevant genes. Pathological analysis showed significant regression (≥50%) after pazopanib treatment in only one undifferentiated (pleomorphic) sarcoma. NGS analyses revealed a very high frequency of CDK4 amplification (88%, 7/8) in the group of dedifferentiated liposarcoma. In addition, two potentially druggable mutations, a MAP2K1 missense mutation (E203K) and a BRAF missense mutation (V600E), were traceable in two undifferentiated (pleomorphic) sarcoma patients (11%, 2/18). Our findings demonstrate that NGS testing is a powerful technology helping to improve diagnostic accuracy and offering some patients the chance for personalized medicine even in a “mutation unlikely” cohort like STS.

Upper gastrointestinal carcinomas comprise squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus, as well as gastric AC [...]

Background: The aim of this study was to evaluate postoperative morbidity, mortality, and failure to rescue following complications after radical resection for gastric cancer. Methods: A retrospective analysis of the surgical database of patients with gastroesophageal malignancies at our institution was performed. All consecutive patients undergoing R0 gastrectomy for pT1&ndash, 4 M0 gastric adenocarcinoma between October 1972 and February 2014 were eligible for this analysis. Patients were divided into two groups according to the date of surgery: an early cohort operated on from 1972&ndash, 1992 and a late cohort operated on from 1993&ndash, 2014. Both groups were compared regarding patient characteristics and surgical outcomes. Results: A total of 1107 patients were included. Postoperative mortality was more than twice as high in patients operated on from 1972&ndash, 1992 compared to patients operated on from 1993&ndash, 2014 (6.8% vs. 3.2%, p = 0.017). Between both groups, no significant difference in failure to rescue after major surgical complications was observed (20.8% vs. 20.5%, p = 1.000). Failure to rescue after other surgical and non-surgical complications was 37.8% in the early cohort compared to 3.2% in the late cohort (p &lt, 0.001). Non-surgical complications accounted for 71.2% of lethal complications between 1972 and 1992, but only for 18.2% of lethal complications between 1993 and 2014 (p = 0.002). Conclusion: In the course of four decades, postoperative mortality after radical resection for gastric cancer has more than halved. In this cohort, the reason for this decrease was reduced mortality due to non-surgical complications. Major surgical morbidity after gastrectomy remains challenging.

Introduction: Survival in gastric cancer is often limited by peritoneal carcinomatosis, which supposedly develops from serosal tumor infiltration or tumor cell spread during gastrectomy with lymphadenectomy. To eliminate peritoneal tumor cells, extensive intraperitoneal lavage (EIPL) has been suggested. Impressive results have been achieved in Japanese trials. In this trial, we assessed EIPL in Western patients. Methods: This prospective trial included patients with non-metastatic gastric adenocarcinoma undergoing gastrectomy with D2 lymphadenectomy. Peritoneal fluid samples at laparotomy, after lymphadenectomy, and after EIPL were analyzed for tumor cells using cytology and EpCAM antibodies. The primary endpoint was peritoneal conversion rate (PCR; proportion of patients in whom EIPL eliminated tumor cells after lymphadenectomy). Secondary endpoints were peritoneal release rate (PRR; proportion of patients with peritoneal tumor cells after gastrectomy/lymphadenectomy among all patients without cells before gastrectomy/lymphadenectomy) and prevalence of peritoneal tumor cells before resection. EIPL was considered ineffective if PCR ⩽ 0.2 and warranted further exploration if PCR ⩾ 0.5. Clinicaltrials.gov identifier is NCT01476553. Results: The trial was stopped early because tumor cells after gastrectomy/lymphadenectomy were detected in only 3/27 (11.1%) patients. In none of these did EIPL eliminate tumor cells (PCR 0, 95% confidence interval [CI] 0%–12.5%). In 8/27 (29.6%) patients, tumor cells were detected after EIPL. PRR was 11.1% (95% CI 2.4%–29.2%). There were no perioperative complications higher than Clavien-Dindo grade 3a. Conclusions: In Western patients, free peritoneal tumor cells after gastrectomy with D2 lymphadenectomy for gastric cancer were detected only sporadically. Although based on few cases, the findings suggest that EIPL spreads tumor cells into the peritoneal cavity, thus being potentially harmful. Therefore, EIPL cannot be generally recommended.

Neovascularisation is a critical step in the progression of malignant tumors. Circulating endothelial progenitor cells (cEPC) have been proposed as surrogate markers of vasculogenesis in malignancies. In this project, we studied the impact of tumor-specific therapy on cEPC and associated angiogenic factors in patients with soft tissue tumors.Fifty-three patients with soft tissue tumors (25 soft tissue sarcomas, 19 GIST, 9 desmoids) and 15 healthy controls were included. Blood samples were obtained at two time points, before and 8 weeks after start of tumor-specific therapy. Peripheral blood mononuclear cells (PBMCs) were isolated. cEPCs were characterised as CD34VEGF-A and Ang-2 concentrations were significantly higher in tumor patients than in healthy controls in both samples (p .01). Sarcoma patients with progressive disease developed a significant increase in cEPC levels between the two blood samples compared to those with stable disease (p = .002). GIST patients with progressive tumor or metastatic disease showed significant increase in VEGF-A values (p = .01).The pre-treatment values of the angiogenic markers did not correlate with the clinical course of the disease. However, cEPCs levels were significantly higher in sarcoma patients with progressive disease compared to those with stable disease and should be further evaluated as early markers of disease progression in sarcoma patients. VEGF-A and angiopoetin-2 clearly play a role as mediators of the vasculogenesis contributing to tumor progression.

Objective In this article, we outline the important features of pancreatic cancer surgery in cases with visceral artery encasement. Background Despite recent advances in diagnosis and treatment, pancreatic cancer continues to have a poor prognosis. Due to its limited response to chemotherapies, radiation, or targeted therapies, surgery (in combination with adjuvant chemotherapy) is the only potential way to treat pancreatic cancer in a curative manner. As only about 20% of the patients have surgically resectable disease at the time of diagnosis, the resection of encased visceral veins and arteries, along with neoadjuvant regimens, is one approach to treat otherwise palliative patients. Methods Based on a selective literature review, we discuss the results of several studies and meta-analyses, comparing the mortality and morbidity, as well as long-term survival in patients undergoing arterial resection vs standard treatment. We conducted a selective literature review in PubMed without restrictions regarding time of publication or study design. Only articles in English language were selected. Conclusions Several studies and meta-analyses comparing resection with and without arterial resection and reconstruction showed a significantly higher post-operative mortality and morbidity and shorter long-term survival in patients who required arterial resection. In patients with tumors initially considered irresectable, the approach of neoadjuvant chemotherapy followed by resection with arterial reconstruction showed a significantly increased survival compared to palliative chemotherapy alone with acceptable postoperative morbidity. Tumor resection with arterial reconstruction following intensive preoperative chemotherapy (plus radiochemotherapy in some cases) should be considered in selected patients, as it can prolong survival and potentially lead to sustained freedom from tumor recurrence.

The purpose of this study was to investigate clinical features, prognostic factors, and overall survival (OS) in surgical patients with gastric remnant cancer (GRC).A retrospective analysis of patients with gastrectomy for pT1-4 gastric cancer between October 1972 and February 2014 at our institution was performed. Clinical characteristics were compared between patients with GRC and those with primary gastric cancer (PGC). Multivariable Cox regression analysis was performed to determine the prognostic factors for OS in patients with GRC. A propensity score-matched cohort was used to investigate OS between the GRC and PGC groups.Of a baseline cohort of 1440 patients, 95 patients with GRC were identified. Patients with GRC underwent more multivisceral resections (p 0.001) than patients with PGC despite lower tumor stages (p = 0.018); however, R0 resection rates were not significantly different (p = 0.211). The postoperative overall (p = 0.032) and major surgical (p = 0.021) complication rates and the 30-day (p = 0.003) and in-hospital (p = 0.008) mortality rates were higher in patients with GRC. In multivariable analysis, the only prognostic factors for worse OS in GRC were higher tumor stage (p 0.001) and the occurrence of postoperative complications (p 0.001). OS between propensity score-matched GRC and PGC groups was not significantly different (p = 0.772).GRC required more invasive surgery than PGC; however, the feasibility of R0 resection was similar. The prognostic factors of GRC were similar to those of PGC, and OS was not significantly different between both groups. Patients with GRC benefit from extensive surgery when performed with low morbidity and mortality.

Purpose Improvement of the therapeutic approaches in gastrointestinal stromal tumors (GIST) by the introduction of targeted therapies requires appropriate diagnostic tools, which allow sufficient assessment of therapeutic response, including differentiation of true progression from pseudoprogression due to myxoid degeneration or intratumoral hemorrhage. In this literature review the impact and limitations of different imaging modalities used in GIST therapy monitoring are discussed. Methods PubMed and Cochrane library search were performed using appropriate keywords. Overall, 39 original papers fulfilled the defined criteria and were included in this systematic review. Results Morphological imaging modalities like computed tomography (CT) are primarily used for both diagnosis and therapy monitoring. However, therapy with tyrosine kinase inhibitors and other targeted therapies in GIST may lead only to a minor tumor volume reduction even in cases of response. Therefore, the use of Response Evaluation Criteria in Solid Tumors (RECIST) has limitations. To overcome those limitations, modified response criteria have been introduced for the CT-based therapy assessment, like the Choi criteria as well as criteria based on dual energy CT studies. Functional imaging techniques, mostly based on FDG PET-CT are in use, in particular for the assessment of early treatment response. Conclusions The impact and the limitations of PET-based therapy monitoring, as well as its comparison with CT, MRI and survival data are discussed in this review. CT is still the standard method for the evaluation of therapy response despite its several limitations. FDG PET-CT is helpful for the assessment of early therapy response; however, more prospective data are needed to define its role as well as the appropriate time intervals for therapy monitoring. A multiparametric evaluation based on changes in both morphological and functional data has to be assessed in further prospective studies.

Background: The aim of this study was to investigate the impact of postoperative complications on overall survival (OS) after radical resection for gastric cancer. Methods: A retrospective analysis of our institutional database for surgical patients with gastroesophageal malignancies was performed. All consecutive patients who underwent R0 resection for M0 gastric cancer between October 1972 and February 2014 were included. The impact of postoperative complications on OS was evaluated in the entire cohort and in a subgroup after exclusion of 30 day and in-hospital mortality. Results: A total of 1107 patients were included. In the entire cohort, both overall complications (p &lt, 0.001) and major surgical complications (p = 0.003) were significant risk factors for decreased OS in univariable analysis. In multivariable analysis, overall complications were an independent risk factor for decreased OS (p &lt, 0.001). After exclusion of patients with complication-related 30 day and in-hospital mortality, neither major surgical (p = 0.832) nor overall complications (p = 0.198) were significantly associated with decreased OS. Conclusion: In this study, postoperative complications influenced OS due to complication-related early postoperative deaths. In patients successfully rescued from early postoperative complications, neither overall complications nor major surgical complications were risk factors for decreased survival.

The outcome of high-risk soft tissue sarcoma (STS) is poor with radical surgery being the only potentially curative modality. Pazopanib is a multikinase inhibitor approved for the treatment of metastatic STS. Herein, in terms of the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS) trial, we evaluate the potential role of kinetic analysis of fludeoxyglucose F-18 (18F-FDG) data derived from the application of dynamic positron emission tomography/computed tomography (PET/CT) in response assessment to pazopanib of STS patients scheduled for surgical resection. Sixteen STS patients treated with pazopanib as neoadjuvant therapy before surgery were enrolled in the analysis. All patients underwent dynamic PET/CT prior to and after pazopanib treatment. Data analysis consisted of visual (qualitative) analysis of the PET/CT scans, semi-quantitative evaluation based on standardized uptake value (SUV) calculations, and quantitative analysis of the dynamic 18F-FDG PET data, based on two-tissue compartment modeling. Resection specimens were histopathologically assessed and the percentage of regression grade was recorded in 14/16 patients. Time to tumor relapse/progression was also calculated. In the follow-up, 12/16 patients (75%) were alive without relapse, while four patients (25%) relapsed, among them one patient died. Median histopathological regression was 20% (mean 26%, range 5&ndash, 70%). The studied population was dichotomized using a histopathological regression grade of 20% as cut-off. Based on this threshold, 10/14 patients (71%) showed partial remission (PR), while stable disease (SD) was seen in the rest 4 evaluable patients (29%). Semi-quantitative evaluation showed no statistically significant change in the widely used PET parameters, SUVaverage and SUVmax. On the other hand, 18F-FDG kinetic analysis revealed a significant decrease in the perfusion-related parameter K1, which reflects the carrier-mediated transport of 18F-FDG from plasma to tumor. This decrease can be considered as a marker in response to pazopanib in STS and could be due to the anti-angiogenic effect of the therapeutic agent.

4533 Background: Disease-free survival (DFS) is an appealing surrogate endpoint for overall survival (OS) in trials on neoadjuvant or adjuvant cancer therapy, because it is available faster and with less follow-up effort. The aim of this study was to assess if DFS can be a valid surrogate endpoint for OS when comparing neoadjuvant treatment followed by surgery to surgery alone for gastroesophageal adenocarcinoma. Methods: Individual patient data (IPD) from eight randomized controlled trials (n = 1,126 patients) which compared neoadjuvant therapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma were used for the analysis. Correlation between OS-time and DFS-time was calculated. Kaplan-Meier survival curves and corresponding hazard ratios (HRs) for treatment effects were separately determined for each trial. Subsequently, HRs were pooled in a meta-analysis using a random-effects model. An error-in-variables linear regression model was used to compare observed and predicted values. The minimum treatment effect on DFS necessary to predict a non-zero treatment effect on OS was estimated by calculating the surrogate threshold effect. Results: OS-time correlated strongly with DFS-time. HRs for OS and DFS were highly similar for all single trials. The meta-analysis yielded almost identical overall HRs for treatment effects on OS and DFS. The determination coefficient for the association between HRs for OS and DFS was 0.912 (95% confidence interval 0.75-1.0), indicating a strong trial-level surrogacy between OS and DFS. The surrogate threshold effect was calculated at 0.79, indicating that a future trial yielding a hazard ratio for the treatment effect on DFS < 0.79 could be expected with a 95% probability to yield a hazard ratio for the treatment effect on OS < 1. Conclusions: DFS and OS strongly correlate both after neoadjuvant therapy followed by surgery and after surgery alone for gastroesophageal adenocarcinoma. Likewise, the treatment effects on the two endpoints are very similar. Consequently, DFS can be regarded an appropriate surrogate endpoint for OS in trials on neoadjuvant therapy for gastroesophageal adenocarcinoma.

// Ulrich Ronellenfitsch 1,* , Christiane Lippert 2,* , Rainer Grobholz 3 , Siegfried Lang 4 , Stefan Post 1 , Georg Kahler 1 and Timo Gaiser 2 1 Department of Surgery, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany 2 Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany 3 Institute of Pathology, Kantonsspital Aarau, Aarau, Switzerland 4 First Department of Medicine, Division of Biostatistics, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany * These authors have contributed equally to this work Correspondence to: Timo Gaiser, email: // Keywords : early gastric cancer, lymph node metastases, histopathological risk factors, endoscopic treatment, Western study population Received : October 21, 2015 Accepted : January 24, 2016 Published : February 06, 2016 Abstract Background: Selected cases of early gastric cancer (EGC) can be successfully treated by endoscopic therapy if the risk of concurrent lymph node metastases (LNM) is negligible. Criteria for endoscopic resection based on risk factor analyses for LNM have been established mainly in Asia. However, it is not clear to what extent these recommendations can be transferred to Western collectives. The aim of this study was to analyze predictors for LNM in EGC in a Western study population. Methods: From our institutional archive, we selected all patients with gastric adenocarcinoma who had undergone gastrectomy with lymphadenectomy (1972 – 2005). Among 1970 patients 275 cases with EGC were identified. Clinical and pathological data were collected and logistic regression analyses performed. Results: LNM were present in 36/275 (13.1%) patients. With deeper invasion proportion of LNM increased. At submucosa level (sm1), patients were almost five times more likely to have LNM than at mucosa levels. Multivariable logistic regression analysis revealed lymphovascular invasion, diffuse- and mixed-type, and invasion depth as significant independent histopathological predictors of LNM. In patients with intestinal type according to Lauren and no lymphovascular invasion, we found only one LNM-positive case out of 43 patients in the pT1b (sm1 and sm2) groups. Conclusions: Our results underline the recommendation of most guidelines that endoscopic resection is sufficient for pT1a ECG because of the low incidence of LNM in this group. However, there seems also a role for endoscopic therapy in cases of pT1b (sm1/2) EGC with intestinal type differentiation and no lymphovascular invasion.

Background. The surgical resection of soft tissue sarcomas (STS) with sciatic nerve involvement presents a significant surgical and oncological challenge. Current treatment strategies pursue a multimodal approach with the aim of limb preservation. We aim to evaluate the outcomes of limb-sparing surgery of STS in a patient cohort and to propose a classification for STS with sciatic nerve involvement. Methods. Patients receiving limb-preserving resections for STS with sciatic nerve involvement between 01/2010 and 01/2017 were included. Clinical and oncological data were prospectively collected in a computerized database and retrospectively analyzed. Sciatic nerve involvement in STS was classified preoperatively as follows: type A for nerve encasement; type B for nerve contact; and type C for no nerve involvement. Results. A total of 364 patients with STS were treated, of which 27 patients had STS with sciatic nerve involvement. Eight patients with type A tumors (29.6%) underwent sciatic nerve resection, and 19 patients with type B tumors (70.4%) received epineural dissections. Disease progression was observed in 8 patients (29.6%) with a local recurrence of 11.1% and distant metastasis in 29.6%. The type of nerve resection significantly influenced leg function but had no impact on disease recurrence or overall survival. Conclusion. In a cohort of carefully selected patients with STS and sciatic nerve involvement, the extent of sciatic nerve resection had no significant impact on disease recurrence or survival. Precise classification of neural involvement may therefore be useful in selecting the appropriate degree of nerve resection, without compromising oncological outcome or unnecessarily sacrificing leg function.

Background Neoadjuvant chemotherapy improves prognosis of patients with locally advanced gastroesophageal adenocarcinoma. The aim of this study was to identify predictors for postoperative survival following neoadjuvant therapy. These could be useful in deciding about postoperative continuation of chemotherapy. Methods This meta-analysis used IPD from RCTs comparing neoadjuvant chemotherapy with surgery alone for gastroesophageal adenocarcinoma. Trials providing IPD on age, sex, performance status, pT/N stage, resection status, overall and recurrence-free survival were included. Survival was calculated in the entire study population and subgroups stratified by supposed predictors and compared using the log-rank test. Multivariable Cox models were used to identify independent survival predictors. Results Four RCTs providing IPD from 553 patients fulfilled the inclusion criteria. (y)pT and (y)pN stage and resection status strongly predicted postoperative survival both after neoadjuvant therapy and surgery alone. Patients with R1 resection after neoadjuvant therapy survived longer than those with R1 resection after surgery alone. Patients with stage pN0 after surgery alone had better prognosis than those with ypN0 after neoadjuvant therapy. Patients with stage ypT3/4 after neoadjuvant therapy survived longer than those with stage pT3/4 after surgery alone. Multivariable regression identified resection status and (y)pN stage as predictors of survival in both groups. (y)pT stage predicted survival only after surgery alone. Conclusion After neoadjuvant therapy for gastroesophageal adenocarcinoma, survival is determined by the same factors as after surgery alone. However, ypT stage is not an independent predictor. These results can facilitate the decision about postoperative continuation of chemotherapy in pretreated patients.

IMPORTANCE: Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. OBJECTIVE: To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. DESIGN, SETTING, AND PARTICIPANTS: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. INTERVENTIONS: Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. RESULTS: In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P

(1) Background: Oncological gastrectomy requires complex multidisciplinary management. Clinical pathways (CPs) can potentially facilitate this task, but evidence related to their use in managing oncological gastrectomy is limited. This study evaluated the effect of a CP for oncological gastrectomy on process and outcome quality. (2) Methods: Consecutive patients undergoing oncological gastrectomy before (n = 64) or after (n = 62) the introduction of a CP were evaluated. Assessed parameters included catheter and drain management, postoperative mobilization, resumption of diet and length of stay. Morbidity, mortality, reoperation and readmission rates were used as indicators of outcome quality. (3) Results: Enteral nutrition was initiated significantly earlier after CP implementation (5.0 vs. 7.0 days, p &lt, 0.0001). Readmission was more frequent before CP implementation (7.8% vs. 0.0%, p = 0.05). Incentive spirometer usage increased following CP implementation (100% vs. 90.6%, p = 0.11). Mortality, morbidity and reoperation rates remained unchanged. (4) Conclusions: After implementation of an oncological gastrectomy CP, process quality improved, while indicators of outcome quality such as mortality and reoperation rates remained unchanged. CPs are a promising tool to standardize perioperative care for oncological gastrectomy.

Hintergrund Sowohl retroperitoneale Sarkome (RPS) als auch gastrointestinale Stromatumoren (GIST) sind seltene Tumorentitaten. Ihre chirurgischen Therapieprinzipien unterscheiden sich signifikant von denen anderer Tumorentitaten.

The best surgical approach for tumors of the proximal stomach remains controversial. For proximal gastrectomy (PG), the evidence regarding quality of life (QoL) and functional outcomes is controversial. Moreover, there are limited data from non-Asian settings. All patients who underwent PG from September 2005 to July 2013 were identified from an institutional database. Demographic, perioperative and pathologic characteristics were retrieved. Symptom scores (0 = best/4 = worst) for reflux symptoms, dysphagia and validated QoL metrics (FACT scale, where a higher score is better) were assessed during early and late follow-up. Eligible patients for analysis were those with no evidence of recurrence. Of 465 upper gastrointestinal cancer resections, 50 were PG for adenocarcinoma (42; 84 %), neuroendocrine carcinoma (5; 10 %) or other pathologies (3; 6 %). R0 resection was achieved in 44 (89.8 %) of 49 patients with malignant tumors. Median lymph node collection was 32 (range 7–57). QoL scores did not differ from preoperative to early follow-up but increased compared to both at late follow-up [preoperative, 125 (interquartile range 105–140); early follow-up, 122.5 (97–142); late follow-up, 147 (132–159); p

Faecal immunochemical tests (FITs) for haemoglobin are increasingly used for non-invasive screening for colorectal cancer (CRC) but large scale comparative studies of different FITs for detection of CRC, overall and by stage, are sparse. We aimed to determine and compare performance of different FITs for the detection of CRC, and to assess their stage-specific sensitivities.We assessed sensitivity, specificity and their corresponding 95% confidence intervals for six qualitative FITs among 74 CRC cases (59% stage I or II cancers) and 1480 controls free of colorectal neoplasm. Overall and stage-specific receiver operating characteristic curves were derived for three quantitative FITs. The areas under the curves (AUCs) were calculated and compared.Pairs of overall sensitivity and specificity of the qualitative FITs ranged from 66% and 96% to 92% and 62%, respectively. For the three quantitative tests, AUCs ranged from 0.90 to 0.92, with sensitivities ranging from 80% to 87% at cut-offs yielding 90% specificity. AUCs ranged from 0.85 to 0.92, 0.94 to 0.96, and 0.86 to 0.93 for stage I, stage II and advanced stages (stage III and IV) cancers, respectively. At a specificity of 90%, the tests detected 65%-85% of stage I cancers.The diagnostic performance of FITs regarding detection of CRC is promising, even though the pre-defined cut-offs of some of the qualitative FITs need to be adjusted to limit false-positive rates in screening setting. At cut-off levels yielding 90% specificity, the quantitative tests detected the vast majority of CRCs, even at early stages.

The rectum is a rare site of gastrointestinal stromal tumor (GIST), and factors determining long-term outcome remain unclear. In a population study, we assessed the outcome of rectal GIST patients treated at two referral centers.A total of 39 patients diagnosed with rectal GIST between January 2002 and December 2010 were identified in prospective databases. Tumor and patient characteristics, treatment details, and outcome were evaluated. Median follow-up was 41 (3-110) months.A male predominance was noticed (M/F = 29/10). Median age was 53 years (range, 32-80 years). The cohort included, of 39 patients, 12 low-risk, 26 high-risk, and 1 with M1 disease. Of 38 patients with nonmetastatic disease, 36 underwent surgery as transabdominal (15 of 36) or local (21 of 36) resection. There were 21 patients who received preoperative and/or postoperative imatinib treatment. Patients with preoperative imatinib (16 of 36) had a significantly higher rate of R0 resections (p = .02). Five patients developed local recurrences. All of them had undergone local tumor excision with positive margins and without perioperative imatinib. Also, five patients suffered from distant metastases. All belonged to the high-risk group and underwent tumor surgery (3 R0, 2 R1) without receiving perioperative imatinib. A total of three patients died of disease. Perioperative imatinib was associated with improved local disease-free, disease-free, and overall survival (p.01, p.01, and p = .03, respectively). Local disease-free survival was significantly improved by negative resection margins (p.01).Complete resection is recommended to achieve local disease control. Preoperative imatinib was associated with improved surgical margins. Perioperative imatinib was associated with improved local disease-free, disease-free, and overall survival.

Introduction: Neoadjuvant chemotherapy regimens have been proven to decrease tumour size and stage and significantlyimprove progression-free and overall survival in the treatment of locoregional advanced gastroesophagealadenocarcinomas. Therefore, the pre-therapeutic staging of the tumour extension is of utmost importance for stratificationof patients into this individualized therapy regimen. Within the last years most experience has been gainedusing endoscopic ultrasound (EUS) and it has been considered as a valuable tool for the assessment of locoregionaldisease.Aim: To evaluate the accuracy of endoscopic ultrasound for the preoperative staging of locally advanced gastroesophagealadenocarcinomas with regard to defining patients’ eligibility for neoadjuvant chemotherapy.Material and methods: Between January 2006 and June 2007 consecutive patients (n = 47) who underwent resectionof a gastroesophageal adenocarcinoma and would have been potentially eligible for neoadjuvant chemotherapy wereincluded in this study. Preoperative EUS staging was compared to the postoperative histopathology results. Furthermore,the specificity, sensitivity and positive and negative predictive values for serosal invasion and/or lymph nodepositivity as an eligibility criterion for neoadjuvant chemotherapy were evaluated.Results: Thirty-seven patients were included in the analysis with adenocarcinomas of the distal oesophagus (n = 7),the oesophagogastric junction (n = 8) and the stomach (n = 22). The overall accuracy for predicting the T stage was64.9% (n = 24) with an over- and understaging of 13.5% (n = 5) and 21.6% (n = 8), respectively. The overall accuracyfor predicting the N stage was 64.7% (n = 22), with an over- and understaging of 26.5% (n = 9) and 8.8% (n = 3).Twenty-five out of 37 patients would have met the eligibility criteria for enrolment in a neoadjuvant chemotherapyregimen. The sensitivity was 76% (n = 19/25). The specificity was 75% (n = 9/12). The positive predictive value was86.4%. The negative predictive value was 60%.Conclusions: In this series the sensitivity and specificity of EUS for identification of patients eligible for neoadjuvantchemotherapy seem acceptable. Especially the positive predictive value, which expresses the probability that a patientidentified by EUS as eligible for neoadjuvant chemotherapy met the corresponding histopathological criteria, was high(86.4%). Therefore, it seems justified to apply neoadjuvant chemotherapy in patients identified as eligible by EUS. This underpins the importance of EUS in the staging of gastroesophageal carcinoma. In patients with a “negative” EUS result,the staging needs to be complemented by additional diagnostic modalities such as CT, PET or laparoscopy to facilitatethe correct identification of patients who meet the histopathological inclusion criteria for neoadjuvant chemotherapy.

Introduction For resectable soft tissue sarcoma (STS), radical surgery, usually combined with radiotherapy, is the mainstay of treatment and the only potentially curative modality. Since surgery is often complicated by large tumour size and extensive tumour vasculature, preoperative treatment strategies with the aim of devitalising the tumour are being explored. One option is treatment with antiangiogenic drugs. The multikinase inhibitor pazopanib, which possesses pronounced antiangiogenic effects, has shown activity in metastatic and unresectable STS, but has so far not been tested in the preoperative setting. Methods and analysis This open-label, multicentre phase II window-of-opportunity trial assesses pazopanib as preoperative treatment of resectable STS. Participants receive a 21-day course of pazopanib 800 mg daily during wait time for surgery. Major eligibility criteria are resectable, high-risk adult STS of any location, or metachronous solitary STS metastasis for which resection is planned, and adequate organ function and performance status. The trial uses an exact single-stage design. The primary end point is metabolic response rate (MRR), that is, the proportion of patients with >50% reduction of the mean standardised uptake value (SUV mean ) in post-treatment compared to pre-treatment fluorodeoxyglucose positron emission tomography CT. The MRR below which the treatment is considered ineffective is 0.2. The MRR above which the treatment warrants further exploration is 0.4. With a type I error of 5% and a power of 80%, the sample size is 35 evaluable patients, with 12 or more responders as threshold. Main secondary end points are histopathological and MRI response, resectability, toxicity, recurrence-free and overall survival. In a translational substudy, endothelial progenitor cells and vascular epithelial growth factor receptor are analysed as potential prognostic and predictive markers. Ethics and dissemination Approval by the ethics committee II, University of Heidelberg, Germany (2012-019F-MA), German Federal Institute for Drugs and Medical Devices (61-3910-4038155) and German Federal Institute for Radiation Protection (Z5-22463/2-2012-007). Trial registration number NCT01543802, EudraCT: 2011-003745-18; Pre-results.

Background: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma, but has not yet been evaluated in the context of resectable patients. Here we report findings from the phase 2 part of the phase 2/3 FLOT4 trial, which compared histopathological regression in patients treated with a docetaxel-based triplet chemotherapy versus an anthracycline-based triplet chemotherapy before surgical resection.Methods: In this randomised, open-label, phase 2/3 study, eligible participants were recruited from 28 German oncology centres. Patients with resectable gastric or gastro-oesophageal junction cancer who had clinical stage cT2 or higher, nodal positive (cN+) disease, or both were randomly assigned (1:1) to either three preoperative and three postoperative 3-week cycles of intravenous epirubicin 50 mg/m2on day 1, intravenous cisplatin 60 mg/m2on day 1, and either fluorouracil 200 mg/m2as continuous intravenous infusion or capecitabine 1250 mg/m2orally (two doses of 625 mg/m2per day) on days 1 to 21 (ECF/ECX group) or four preoperative and four postoperative 2-week cycles of docetaxel 50 mg/m2, intravenous oxaliplatin 85 mg/m2, intravenous leucovorin 200 mg/m2, and fluorouracil 2600 mg/m2as a 24 h infusion, all on day 1 (FLOT group). Randomisation was done centrally with an interactive web-response system based on a sequence generated with blocks (block size 2) stratified by Eastern Cooperative Oncology Group performance status, location of primary tumour, age, and nodal status. No masking was done. Central assessment of pathological regression was done according to the Becker criteria. The primary endpoint was pathological complete regression (tumour regression grade TRG1a) and was analysed in the modified intention-to-treat population, defined as all patients who were randomly assigned to treatment excluding patients who had surgery but did not provide resection specimens for central evaluation. The study (including the phase 3 part) has completed enrolment, but follow-up is ongoing and this is an interim analysis. The trial is registered with ClinicalTrials.gov, number NCT01216644. Findings: Between Aug 18, 2010, and Aug 10, 2012, 300 patients (152 patients in the ECF/ECX group; 148 patients in the FLOT group) were enrolled into the phase 2 part of the study, 265 of whom (137 in the ECF/ECX group; 128 in the FLOT group) were assessable on a modified intention-to-treat basis. 119 (93%) of 128 patients in the FLOT group and 126 (92%) of 137 patients in the ECF/ECX group were given all planned preoperative cycles of treatment. FLOT was associated with significantly higher proportions of patients achieving pathological complete regression than was ECF/ECX (20 [16%; 95% CI 10-23] of 128 patients vs eight [6%; 3-11] of 137 patients; p=0·02). 44 (40%) of 111 patients in the ECF/ECX group and 30 (25%) of 119 patients in the FLOT group had at least one serious adverse event involving a perioperative medical or surgical complication. The most common non-surgical grade 3-4 adverse events were neutropenia (52 [38%] of 137 patients in the ECF/ECX group vs 67 [52%] of 128 patients in the FLOT group), leucopenia (28 [20%] vs 36 [28%]), nausea (23 [17%] vs 12 [9%]), infection (16 [12%] vs 15 [12%]), fatigue (19 [14%] vs 11 [9%]), and vomiting (13 [10%] vs four [3%]). Interpretation: Perioperative FLOT was active and feasible to administer, and might represent an option for patients with locally advanced, resectable gastric or gastro-eosophageal junction adenocarcinoma.

This study aimed to compare mortality from cancers between ethnic German immigrants and the native German population. We conducted a retrospective cohort study of 34,393 so-called Aussiedler from the Former Soviet Union in Germany's largest federal state and ascertained vital status and cause-of-death through population registries. We used direct and indirect standardisation to compare Aussiedler, German and Russian federation rates, and Poisson regression for influencing factors. Compared to Germans, male Aussiedler had similar all-cancer mortality, standardised mortality ratio (SMR) 0.97 (95% confidence interval: 0.86-1.10), higher mortality from lung and stomach cancers, and lower mortality from prostate cancer; SMR 0.48 (0.25-0.84). Females had lower all-cancer, lung, and breast cancer mortality with SMR (95% CI), 0.76 (0.67-0.89), 0.61 (0.34-1.01) and 0.47 (0.29-0.70), respectively. Compared to the Russian Federation, Aussiedler had lower all-cancer mortality; males had similar mortality from lung cancers. Better health care in Germany could have resulted in reduced mortality from certain cancers among Aussiedler.

Antiangiogenic substances and radiation therapy (RT) may have synergistic effects and improve irradiation efficacy. We present a cohort study evaluating the toxicity of combined sunitinib and RT as neoadjuvant treatment of extremity and retroperitoneal soft tissue sarcoma (STS). Sixteen patients with locally advanced extremity (6/16) or retroperitoneal (10/16) STS were treated with continuous-dosing sunitinib (15/16: 37.5 mg daily; 1/16: 25 mg daily) and standard RT (45–50.4 Gy) preoperatively. Surgery was scheduled 5–9 weeks following neoadjuvant treatment. The primary goal of the study was to determine combined treatment toxicity according to the Common Terminology Criteria for Adverse Events. Secondary goals were the evaluation of postoperative morbidity and treatment response. Eight of 16 patients developed grade 3, and one patient developed grade 4, hematological toxicity. One patient experienced grade 3 hand–foot syndrome. The most frequent treatment toxicities of any grade were hematological (15/16) or dermatological (9/16). Three patients had partial response, 11 had stable disease, and 2 had progressive disease according to Response Evaluation Criteria in Solid Tumors (RECIST). Fourteen of 16 patients underwent surgery; tumors were not removed in two patients because of patient refusal or intercurrent metastatic disease. The proportion of tumor necrosis exceeded 90 % in 5 of 14 patients, and 4 patients had postoperative complications requiring reintervention. Preoperative treatment with concurrent sunitinib and RT was tolerable, and postoperative morbidity did not increase. Combined treatment with RT and sunitinib was also feasible in patients with retroperitoneal STS, and warrants further investigation.

Background The prognosis of patients with gastroesophageal adenocarcinoma is poor. There is conflicting evidence regarding effects of preoperative chemotherapy on survival and other outcomes. Methods We conducted a meta-analysis with aggregate and individual patient data (IPD) to assess the effect of preoperative chemotherapy for gastroesophageal adenocarcinoma on survival and other outcomes. Two independent reviewers identified eligible randomised controlled trials (RCTs) comparing chemotherapy+/-radiotherapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma. IPD was solicited from all trials. Meta-analyses were performed using the two stage method. Results We identified 14 RCTs (2422 patients). For eight RCTs (1049 patients; 43.3%) we obtained IPD. Preoperative chemotherapy was associated with longer overall survival (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.73-0.89; p < 0.0001). There were larger treatment effects in tumours of the gastroesophageal junction and for chemoradiotherapy compared to chemotherapy, but the tests for subgroup differences were not statistically significant. Preoperative chemotherapy was associated with longer disease-free survival, higher likelihood of R0 resection and more favourable post-treatment tumour stage, but not perioperative complications. Conclusion Preoperative chemotherapy for locoregional gastroesophageal adenocarcinoma increases survival compared to surgery alone. It should be offered to all eligible patients. There appear to be larger survival advantages in tumours of the gastroesophageal junction and for chemoradiotherapy, but these findings require prospective confirmation.

Background: The outcome of patients with locally advanced gastroesophageal adenocarcinoma (adenocarcinoma of the esophagus, gastroesophageal (GE) junction, and stomach) is poor. There is conflicting evidence regarding the effects of perioperative chemotherapy on survival and other outcomes. Objectives: To assess the effect of perioperative chemotherapy for gastroesophageal adenocarcinoma on survival and other clinically relevant outcomes in the overall population of participants in randomized controlled trials (RCTs) and in prespecified subgroups. Search methods: We performed computerized searches in the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Review of Effectiveness (DARE), the Cochrane Database of Systematic Reviews (CDSR) from The Cochrane Library, MEDLINE (1966 to May 2011), EMBASE (1980 to May 2011), and LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), combining the Cochrane highly sensitive search strategy with specific search terms. Moreover, we handsearched several online databases, conference proceedings, and reference lists of retrieved papers. Selection criteria: We included RCTs which randomized patients with gastroesophageal adenocarcinoma, in the absence of distant metastases, to receive either chemotherapy with or without radiotherapy followed by surgery, or surgery alone. Data collection and analysis: Two independent review authors identified eligible trials. We solicited individual patient data (IPD) from all selected trials. We performed meta-analyses based on intention-to-treat populations using the two-stage method to combine IPD with aggregate data from RCTs for which IPD were unavailable. We combined data from all trials providing IPD in a Cox proportional hazards model to assess the effect of several covariables on overall survival. Main results: We identified 14 RCTs with 2422 eligible patients. For eight RCTs with 1049 patients (43.3%), we were able to obtain IPD. Perioperative chemotherapy was associated with significantly longer overall survival (hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.73 to 0.89). This corresponds to a relative survival increase of 19% or an absolute survival increase of 9% at five years. This survival advantage was consistent across most subgroups. There was a trend towards a more pronounced treatment effect for tumors of the GE junction compared to other sites, and for combined chemoradiotherapy as compared to chemotherapy in tumors of the esophagus and GE junction. Resection with negative margins was a strong predictor of survival. Multivariable analysis showed that tumor site, performance status, and age have an independent significant effect on survival. Moreover, there was a significant interaction of the effect of perioperative chemotherapy with age (larger treatment effect in younger patients). Perioperative chemotherapy also showed a significant effect on several secondary outcomes. It was associated with longer disease-free survival, higher rates of R0 resection, and more favorable tumor stage upon resection, while there was no association with perioperative morbidity and mortality. Authors' conclusions: Perioperative chemotherapy for resectable gastroesophageal adenocarcinoma increases survival compared to surgery alone. It should thus be offered to all eligible patients. There is a trend to a larger survival advantage for tumors of the GE junction as compared to other sites and for chemoradiotherapy as compared to chemotherapy in esophageal and GE junction tumors. Likewise, there is an interaction between age and treatment effect, with younger patients having a larger survival advantage, and no survival advantage for elderly patients.

In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy.Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS).Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed.After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity.

The duodenum is a rare site of primary gastrointestinal stromal tumor (GIST). Overall (OS) and disease-free survival (DFS) after limited resection (LR) versus pancreaticoduodenectomy (PD) were studied. All patients who underwent surgery for primary, localized duodenal GIST between 2000 and 2011 were identified from four prospective institutional databases. OS and DFS were calculated by Kaplan–Meier method. Univariate analysis was performed. Eighty-four patients (median follow-up 42 months) underwent LR (n = 56, 67 %) or PD (n = 28, 33 %). Patients in the PD group had a larger median tumor size (7 cm vs. 5 cm, p = 0.024) and higher mitotic count (39 % vs. 19 % >5/50 high-power fields, p = 0.05). Complications were observed in five patients (9 %) in the LR group and ten patients (36 %) in the PD group. OS and DFS for the entire cohort were 89 % and 64 % at 5 years, respectively. No difference in outcome between LR and PD were observed. Eleven patients were treated with preoperative IM. A major RECIST response was obtained in nine (80 %), whereas two had stable disease. Twenty-three patients received postoperative Imatinib (IM). A trend toward a better OS in IM-treated patients could be detected only in the high-risk group. Type of duodenal resection does not impact outcome. The choice should be determined by duodenal site of origin and tumor size. IM may be considered in cases at high risk of recurrence; in neoadjuvant setting, IM might facilitate resection and possibly increase the chance of preserving normal biliary and pancreatic anatomy.

Surgical indication for metastatic gastrointestinal stromal tumor (GIST) treated with imatinib is not yet established.We analyzed 80 patients who underwent surgery for metastatic GIST after imatinib therapy from July 2002 to October 2007. Patients were divided into those with surgery at best clinical response (group A, n = 49) and those with surgery at focal progression (group B, n = 31). Primary end points were progression-free survival (PFS) and disease-specific survival (DSS).Two-year postoperative PFS was 64.4% in group A and 9.7% in group B (P0.01). In group A, median PFS was not reached; in group B, it was 8 months. Median DSS from the time of imatinib onset was not reached in either group. Five-year DSS was 82.9% in group A and 67.6% in group B (P0.01). Multivariate analysis confirmed a significantly shorter PFS and DSS in group B. Surgical morbidity occurred in 13 patients (16.3%).Surgery for focal progressive lesions could be considered as part of the second-line/third-line armamentarium in selected cases. Surgery of residual disease upon best clinical response seems associated with survival benefit compared with historical controls in similar patient collectives treated with imatinib alone. However, evidence from prospective randomized trials is needed to make definite recommendations.

Background Gastrointestinal stromal tumors (GIST) of the esophagogastric junction might pose a major problem to surgical resection. If locally advanced, extended or multivisceral resection with relevant procedural-specific morbidity and mortality is often necessary. Case presentation We report a case of a patient with a locally advanced GIST of the esophagogastric junction who was treated by transhiatal resection of the lower esophagus and gastric cardia with reconstruction by interposition of segment of the jejunum (Merendino procedure). Prior to resection, downsizing of the tumor had successfully been achieved by treatment with imatinib mesylate for six months. Histological proof of GIST by immunohistochemical expression of c-KIT and/or PDGF alpha Receptor is crucial to allow embarking on this treatment strategy. Conclusion A multimodal approach for an advanced GIST of the esophagogastric junction with preoperative administration of imatinib mesylate could avoid extended resection. The Merendino procedure might be considered as the reconstruction method of choice after resection of GIST at this location.

10541 Background: Experimental data indicate that concurrent treatment with anti-angiogenic substances such as sunitinib improves the efficacy of irradiation. The aim of this phase I trial was to e...

10518 Background: Gastrointestinal stromal tumors (GISTs) show KIT or PDGFRα gain-of-function mutations in 85% as the primary oncogenic drivers. Although the use of tyrosine kinase inhibitors (TKI)...

10554 Background: Metastases to the liver and the peritoneum are the typical locations of tumor spread in GIST. Effective 2nd and 3rd line therapies beyond imatinib lead to advanced GIST as a chron...

10566 Background: Due to its low incidence, evidence regarding DT is scarce, and consensus on recommended treatment is difficult to achieve. This study systematically assesses clinical presentation, treatment characteristics and QoL in a large cohort of DT patients (pts). Methods: Demographic and clinical variables were retrieved from a database of 224 pts with histologically confirmed DT presenting to our referral center from 10/04-7/12. For a subset of 46 pts, QoL was assessed with the SF-12 questionnaire. The distribution of variables in the entire pt population and clinically relevant subgroups was calculated and compared with appropriate statistics (t-test, nonparametric tests). Denominators varied due to non-availability of variables for some pts. Results: 153 (68.3%) pts were female. Mean age at first diagnosis was 36.9 (3-73) yrs. Primary tumor site was limb/intraabdominal/rectus abdominis/trunk in 40/43/43/66 (21/22/22/35%) of 192 pts. 65/108 (60%) pts recalled a trauma or medical intervention at the DT site. 38/43 (88%) pts with rectus abdominis DT were female, and 31/38 (82%) had previous pregnancies, median time to DT diagnosis after end of pregnancy was 17 months. Primary therapy was resection/imatinib/tamoxifen/watchful waiting in 136/9/8/7 (83/6/5/4%) pts. Resection was R0/R1/R2 in 47/66/22 (35/49/16%) pts. After R0/R1 resection, DT recurred in 46% and 62% resp. after a median of 356/334 days. Physical/mental SF-12 summary scores were 39.2/40.8, 41.5/45.4, and 48.0/44.5 in pts with limb, intraabdominal, and trunk DT and 38.6/42.6 and 43.3/42.5 in pts with and without recurrence (reference population score 50; all p>0.05 for subgroup comparisons). Five women delivered a healthy child in parallel to clinically existent DT. 56% of our patients are alive with disease, whereas 44% have no evidence of disease. Conclusions: In 83% of DT pts, resection is the first treatment step and is R0 only in one third. 60% of the pts recall trauma/medical intervention at the DT site. Rectus abdominis DT occur after a median of 1.5 yrs after pregnancy. Despite the fact that 56% of our pts live with disease, their QoL is only slightly decreased, with lowest values for physical QoL in pts with recurrence.

10053 Background: It is often recommended to regard patients with a ruptured of GIST as having a very high risk for recurrence. Patients have been entered to phase III adjuvant trials of imatinib. ...