Infiltration Depth is the Most Relevant Risk Factor for Overall Metastases in Early Esophageal Adenocarcinoma.

BACKGROUND: Research in early esophageal adenocarcinoma focused on prediction of lymph node metastases in order to stratify patients for endoscopic treatment instead of esophagectomy. Although distant metastases were described in rates of up to 13% of patients within a follow-up of 3 years, their prediction has been neglected so far. METHODS: In a secondary analysis, a cohort of 217 patients (53 T1a and 164 T1b) treated by esophagectomy was analyzed for histopathological risk factors. Their ability to predict the combination of lymph node metastases at surgery as well as metachronous locoregional and distant metastases (overall metastatic rate) was assessed by uni- and multivariate logistic regression analysis. RESULTS: Tumor invasion depth was correlated with both lymph node metastases at surgery (τ = 0.141; P = .012), tumor recurrences (τ = 0.152; P = .014), and distant metastases (τ = 0.122; P = 0.04). Multivariate analysis showed an odds ratio of 1.31 (95% CI 1.02-1.67; P = .033) per increasing tumor invasion depth and of 3.5 (95% CI 1.70-6.56; P < .001) for lymphovascular invasion. The pre-planned subgroup analysis in T1b tumors demonstrated an even lower predictive ability of lymphovascular invasion with an odds ratio of 2.5 (95% CI 1.11-5.65; P = 0.028), whereas the predictive effect of sm2 (odds ratio 3.44; 95% CI 1.00-11.9; P = 0.049) and sm3 (odds ratio 3.44; 95% CI 1.00-11.9; P = 0.049) tumor invasion depth was similar. CONCLUSIONS: The present report demonstrates the insufficient risk prediction of histopathologic risk factors for the overall metastatic rate.

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study.

BACKGROUND & AIMS: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC. RESULTS: Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P = .41). The odds ratio for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P = .18). CONCLUSIONS: In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.

Complex gastric surgery in Germany-is centralization beneficial? Observational study using national hospital discharge data.

PURPOSE: This observational study explored the association between hospital volume and short-term outcome following gastric resections for non-bariatric indication, aiming to contribute to the discussion on centralization of complex visceral surgery in Germany. METHODS: Based on complete national hospital discharge data from 2010 to 2015, the association between hospital volume and in-hospital mortality was evaluated according to volume quintiles and volume deciles. Case-mix differences regarding surgical indication, age, sex, and comorbidities were considered for risk adjustment. In addition, rates of major complications and failure to rescue were analyzed across hospital volume categories. RESULTS: Inpatient episodes (72,528) with gastric resection were analyzed. Risk-adjusted mortality in patients treated in very low volume hospitals (median volume of 5 surgeries per year) was higher (12.0% [95% CI 11.4 to 12.5]) compared to those treated in very high volume hospitals (50 surgeries per year; 10.6% [10.0 to 11.1]). Failure to rescue patients with complications was 28.1% [27.0 to 29.3] in very low volume hospitals and 22.7% [21.6 to 23.8] in very high volume hospitals. Differences were similar within the subgroup of patients operated for gastric cancer. CONCLUSIONS: Treatment in very high volume hospitals is associated with a lower in-hospital mortality compared to treatment in very low volume hospitals. This effect seems to be determined by the ability to rescue patients who experience complications. As the observed benefit is only related to very high volumes, the results do not clearly indicate that centralization may improve short-term results substantially, unless a very high degree of centralization would be achieved. Possibly, further research focusing on other outcome measures, such as clinical processes or long-term results, might lead to divergent conclusions.

The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III trial of the German AIO/CAO-V/CAOGI.

BACKGROUND: Historical data indicate that surgical resection may benefit select patients with metastatic gastric and gastroesophageal junction cancer. However, randomized clinical trials are lacking. The current RENAISSANCE trial addresses the potential benefits of surgical intervention in gastric and gastroesophageal junction cancer with limited metastases. METHODS: This is a prospective, multicenter, randomized, investigator-initiated phase III trial. Previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) receive 4 cycles of FLOT chemotherapy alone or with trastuzumab if Her2+. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will proceed to randomization. The primary endpoint is overall survival; main secondary endpoints are quality of life assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 22 patients have been enrolled. DISCUSSION: If the RENAISSANCE concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, patients with gastric or GEJ cancer and metastases will no longer be considered candidates for surgical intervention. TRIAL REGISTRATION: The article reports of a health care intervention on human participants and is registered on October 12, 2015 under ClinicalTrials.gov Identifier: NCT02578368 ; EudraCT: 2014-002665-30.

Lymph Node Retrieval is Inferior in the Modified Merendino Resection for Early Barrett's Carcinoma: A Matched-Pair Comparison with Ivor Lewis Resection.

AIM OF THE STUDY: A matched-pair comparison between the modified Merendino resection (MER) and Ivor Lewis resection (ILR) for early Barrett's carcinoma. BACKGROUND: Early adenocarcinoma of the esophagus (eACE) with positive risk factors for lymph node metastasis (LNM) needs surgery for cure. MER appeared to be an alternative to ILR. METHODS: Between July 2000 and July 2012, 156 patients with high-grade dysplasia or eACE received ILR, whereas in 30 cases MER was performed in a tertiary care center for GI Surgery. A matched-pair analysis was performed on the basis of sex, age, BMI, ASA classification and tumor stage. Thirty patients were assigned to each group. The data were analyzed regarding perioperative aspects (e.g., operating time, hospital stay, complications, number of lymph nodes) and survival analysis. RESULTS: The mean operating time was 301.7 min for ILR, compared to 255.4 min for MER (p = 0.044). The hospital stay following ILR was significantly longer than for MER (22.4 days ILR vs. 16.4 days MER, p = 0.023). There was no statistically significant difference regarding complications between the two groups (p = 0.463). The number of resected lymph nodes was significantly lower in the MER group (median 21) compared to the ILR group, where a median of 31 lymph nodes could be removed (p < 0.001). There was no statistically significant difference in overall (p = 0.145) or tumor-specific survival (p = 0.353). CONCLUSIONS: Lymph node retrieval is significantly inferior in the MER. Postoperative complication rates were comparable between the two operating techniques, although the operation time for ILR took longer and these patients required a longer hospital stay. MER should not be applied in cases with high risk of LNM.

Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis.

BACKGROUND: Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma. METHODS: We did a meta-analysis of all genome-wide association studies of Barrett's oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p<5 × 10-8). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches-including functional annotation databases and gene-based and pathway-based methods-to identify pathophysiologically relevant cellular mechanisms. FINDINGS: Our sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10-10), MSRA (rs17749155; p=5·2 × 10-10), LINC00208 and BLK (rs10108511; p=2·1 × 10-9), KHDRBS2 (rs62423175; p=3·0 × 10-9), TPPP and CEP72 (rs9918259; p=3·2 × 10-9), TMOD1 (rs7852462; p=1·5 × 10-8), SATB2 (rs139606545; p=2·0 × 10-8), and HTR3C and ABCC5 (rs9823696; p=1·6 × 10-8). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6 × 10-8) and was independent of Barrett's oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p<10-6) belonged to muscle cell differentiation and to mesenchyme development and differentiation. INTERPRETATION: Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies. FUNDING: US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kröner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council.

ESOPEC: prospective randomized controlled multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (NCT02509286).

BACKGROUND: Recent randomized controlled trials comparing neoadjuvant chemoradiation plus surgery or perioperative chemotherapy plus surgery with surgery alone showed significant survival benefits for combined modality treatment of patients with localized esophageal adenocarcinoma. However, head-to-head comparisons of neoadjuvant chemoradiation and perioperative chemotherapy applying contemporary treatment protocols are lacking. The present trial was initiated to obtain valid information whether neoadjuvant chemoradiation or perioperative chemotherapy yields better survival in the treatment of localized esophageal adenocarcinoma. METHODS/DESIGN: The ESOPEC trial is an investigator-initiated multicenter prospective randomized controlled two-arm trial, comparing the efficacy of neoadjuvant chemoradiation (CROSS protocol: 41.4Gy plus carboplatin/paclitaxel) followed by surgery versus perioperative chemotherapy and surgery (FLOT protocol: 5-FU/leucovorin/oxaliplatin/docetaxel) for the curative treatment of localized esophageal adenocarcinoma. Patients with cT1cN + cM0 and cT2-4acNxcM0 esophageal and junctional adenocarcinoma are eligible. The trial aims to include 438 participants who are centrally randomized to one of the two treatment groups in a 1:1 ratio stratified by N-stage and study site. The primary endpoint of the trial is overall survival assessed with a minimum follow-up of 36 months. Secondary objectives are progression-free survival, recurrence-free survival, site of failure, postoperative morbidity and mortality, duration of hospitalization as well as quality of life. DISCUSSION: The ESOPEC trial compares perioperative chemotherapy according to the FLOT protocol to neoadjuvant chemoradiation according to the CROSS protocol in multimodal treatment of non-metastasized recectable adenocarcinoma of the esophagus and the gastroesophageal junction. The goal of the trial is identify the superior protocol with regard to patient survival, treatment morbidity and quality of life. TRIAL REGISTRATION: NCT02509286 (July 22, 2015).

Pattern of and reason for postoperative residual disease in patients with advanced ovarian cancer following upfront radical debulking surgery.

OBJECTIVE: Describing the pattern of and reasons for post-operative tumor residuals in patients with advanced epithelial ovarian cancer (AOC) operated in a specialized gynecologic cancer center following a strategy of maximum upfront debulking followed by systemic chemotherapy. METHODS: All consecutive AOC-patients treated between 2005 and 2015 due to stages FIGO IIIB/IV were included in this single-center analysis. RESULTS: 739 patients were included in this analysis. In 81 (11.0%) patients, chemotherapy had already started before referral. Of the remaining 658 patients, upfront debulking was indicated in 578 patients (87.8%), while 80 patients (12.8%) were classified ineligible for upfront debulking; mostly due to comorbidities. A complete tumor resection was achieved in 66.1% of the 578 patients with upfront surgery, 25.4% had residuals 1-10mm and 8.5% had residuals exceeding 10mm, and 12.5% of patients had multifocal residual disease. Most common localization was small bowel mesentery and serosa (79.8%), porta hepatis/hepatoduodenal ligament (10.1%), liver parenchyma (4.3%), pancreas (8.0%), gastric serosa (3.2%), and tumor surrounding/infiltrating the truncus coeliacus (2.7%); 14.9% of the patients had non-resectable supra diaphragmatic lesions. Size of residual tumor was significantly associated with progression-free and overall survival. CONCLUSIONS: Upfront debulking for AOC followed by systemic chemotherapy was our main treatment strategy in almost 90% of all patients. The majority experienced a benefit by this approach; while 11.7% of patients probably did not. Understanding sites and reason for residual disease may help to develop adequate surgical training programs but also to identify patients that would better benefit from alternative treatment strategies.

Prognostic risk factors of early gastric cancer-a western experience.

PURPOSE: Lymph node metastasis (LNM) is the leading cause of tumor recurrence in early gastric cancer (EGC). Since endoscopic resection (ER) can be performed in EGC with curative intention when no LNM are present, this study wants to determine the risk factors for LNM in EGC. METHODS: One hundred twenty-four patients who have had an operative resection because of EGC were analyzed. Histopathological workup included tumor infiltration depth, lymphatic and vascular infiltration, lymph node infiltration, tumor differentiation, and the classification of Ming. A complete follow-up was achieved. RESULTS: There was no LNM among tumors meeting the standard or extended criteria for an ER. Lymphatic infiltration (p < 0.001) and infiltration of the submucosal layers (p = 0.018) proved to be the strongest risk factors for LNM. Tumors with a deeper infiltration depth (p = 0.015) and a lower grade of differentiation (p = 0.029) presented with a higher grade of lymphatic infiltration. Tumors located in the body of the stomach (p = 0.003) and tumors with infiltrative growth according to Ming (p = 0.021) had a significantly higher risk for lymphatic infiltration. The 5-year overall survival was 84 % in nodal negative patients and 42 % in patients with LNM (p = 0.002). CONCLUSIONS: ER within the extended criteria with a meticulous histological workup should be performed in EGC to determine whether risk factors for LNM are present. If lymphatic infiltration is observed, surgery with lymphadenectomy is recommended. Tumors exceeding the extended criteria should undergo primary surgery with adequate lymphadenectomy.

The frequency of lymph node metastasis in early-stage adenocarcinoma of the esophagus with incipient submucosal invasion (pT1b sm1) depending on histological risk patterns.

BACKGROUND: A prerequisite for endoscopic treatment (ET) of not only mucosal, but also submucosal early adenocarcinoma of the esophagus (EAC) would be a rate of lymph node (LN) metastasis below the mortality rate of esophagectomy (2-5%). The aim of the present study was to evaluate the rate of LN metastasis in patients with pT1b sm1 EAC. METHODS: 1996-2010, 1,718 patients with suspicion of EAC were referred to the Department of Internal Medicine II at HSK Wiesbaden. In 123/1718 patients, the suspicion (endoscopic ultrasound, EUS) or definitive diagnosis of sm1 EAC (ER/surgery) was made. Rate of LN metastasis was analyzed separately for low-risk (LR; G1-2, L0, V0) and high-risk lesions (HR; G3, L1, V1; ≥ 1 risk factor). LN metastasis was only evaluated in patients who had a proven maximum invasion depth of sm1 (ER and/or surgery), and who in case of ET had a follow-up (FU) by EUS of at least 24 months. RESULTS: Of the 72/123 patients included into the study, 49 patients had LR (68%) and 23 HR lesions (32%). In endoscopically treated LR patients (37/49), mean EUS-FU was 60 ± 30 mo (range 25-146); in HR patients undergoing ET (6/23), it was 63 ± 17 mo (46-86; p = 0.4). Mean number of resected LN was 27 ± 16 (12-62) in operated LR patients and 27 ± 10 (12-47) in HR-patients. The rate of LN metastasis was 2% in the LR (1 patient) and 9% in the HR group (2 patients; p = 0.24). Mortality of esophagectomy was 3%. CONCLUSIONS: The rate of LN metastasis in pT1b sm1 early adenocarcinoma with histological LR pattern was lower than the mortality rate of esophagectomy. ER may therefore be used alternatively to surgery in this group of patients.

Prognostic risk factors of early esophageal adenocarcinomas.

OBJECTIVE: To define prognostic risk factors in patients with early adenocarcinomas of the esophagus (eACEs) who were treated by esophagectomy. BACKGROUND: Although endoscopic resection (ER) is more accepted for eACEs limited to the mucosa, the reported prevalence of lymph node metastases once the tumor infiltrates the submucosa seems to necessitate surgery in these cases. METHODS: We analyzed the results of 168 patients who had an esophageal resection because of an eACE. On the basis of specimen histologies and clinical follow-up (median, 64 months), we investigated the influence of lymph node metastases (N+), tumor infiltration depth, tumor differentiation (G1-3), and lymphatic or venous infiltration (L+ or V+) on overall and tumor-specific survival and recurrence rates. RESULTS: The 5-year survival rate was 79%. Lymph node infiltration was the only prognostic factor for the overall survival [hazard ratio (HR), 2.856; 1.314-6.207; P = 0.008], tumor-specific survival (HR, 8.336; 2.734-25.418; P < 0.001), and tumor recurrence (HR, 8.031; 3.041-21.206; P < 0.001) that was consistently present in all multivariate hazard Cox regression analyses. A total of 47% of the patients who had an N+ status developed tumor recurrences compared with 5.2% of those who had no lymph node involvement (P = <0.001). We found a significant correlation between N+ status and increasing depth of tumor infiltration (P = 0.004), lymphatic vessel infiltration (P = 0.002), tumor differentiation (G1 + G2 vs G3; P = 0.014) and vascular infiltration (P = 0.01). CONCLUSIONS: Lymph node status is the only independent risk factor for survival and recurrence rates. Tumor infiltration depth correlates with the rate of the lymph node metastases, but a clear watershed between deep mucosal and submucosal infiltration does not exist. As a consequence, careful staging procedures, including diagnostic ER, are mandatory to determine which patients can be treated by ER and which require an esophagectomy.

Prognostic and predictive value of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score in surgery for recurrent ovarian cancer.

OBJECTIVES: The Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score was developed as selection criteria and validated as predictor of a high probability for complete resection in recurrent ovarian cancer. It is not defined whether the predictive value is independent from underlying tumor biology or is solely based on a selection of good prognostic risks. METHODS: We performed an exploratory analysis of all consecutive patients with cytoreductive surgery in recurrent ovarian cancer in a tertiary referral center 1999-2013, before and after introduction of the AGO score. RESULTS: 217 consecutive patients were included of whom 112 patients were AGO score positive and 105 patients were score negative. Corresponding complete resection rates were 89.3% and 66.7%, respectively, and confirm the score's predictive value. However, a positive AGO score was also associated with better outcome after adjustment for surgical outcome. Patients with complete resection and a positive AGO score showed a median overall survival of 63.9 months (95% CI 48.1-79.6) compared to 48.4 months (95% CI 30.3-66.5) after complete resection and negative score (log-rank p=0.10). However, in multivariate analysis the only independent prognostic factor was complete resection (HR 2.450; 95% CI: 1.542-3.891). CONCLUSIONS: The AGO score could identify suitable candidates for secondary cytoreductive surgery but failed to prove an independent prognostic value thus suggesting an effect of successful surgery on its own. However, the latter has to be proven prospectively. In addition, further studies should evaluate the predictive and prognostic impact of a negative score.

Quality of life after surgical treatment of early Barrett's cancer: a prospective comparison of the Ivor-Lewis resection versus the modified Merendino resection.

INTRODUCTION: The Merendino (MER) procedure has been evaluated as an alternative to transthoracic esophageal resection (TER) for early stage Barrett's carcinoma. Apart from reducing morbidity and mortality, improvements concerning postoperative health-related quality of life (HRQL) have been postulated. The aim of our study was to compare HRQL between these procedures. MATERIALS AND METHODS: Between July 2000 and July 2007, 117 patients with early Barrett's carcinoma underwent surgery. Patients with tumor recurrence were excluded from the study. HRQL was assessed 1 and 2 years after surgery using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC-QLQ-C30) and the QLQ-OES18 module. Patients recently diagnosed with early Barrett's carcinoma served as controls. Symptoms that showed a difference of more than ten between the control and the study groups were considered clinically relevant and were tested for significant differences between the study groups using the Mann-Whitney U test (p < 0.05). RESULTS: The response rates for the questionnaires ranged between 70 and 93 %. In the MER group, more items reflected a clinical relevant impairment of HRQL than in the TER group. Significant complaints in the MER group included nausea/vomiting, appetite loss, local pain, difficulties with social eating, and choking. Moreover, we found a significant restriction concerning global health and emotional and social functioning in this group 1 year after surgery. 2 years postoperatively, hardly any differences between the operative techniques could be detected. The only symptom in favor of the MER procedure was a better dysphagia score postoperatively. CONCLUSION: Our study suggests that MER procedure is not superior to subtotal esophagectomy with regard to HRQL.

Outcome of immediate re-operation or interval debulking after chemotherapy at a gynecologic oncology center after initially incomplete cytoreduction of advanced ovarian cancer.

BACKGROUND: Prognosis in advanced ovarian cancer is largely determined by completeness of tumor resection achieved during primary surgery. Incomplete initial debulking occurs frequently in non-specialized centers and there is an ongoing discussion about the best time for re-surgery after referral to tertiary centers. METHODS: Patients with advanced epithelial ovarian cancer (FIGO IIIB-IV) admitted between 1999 and 2007 who had primary incomplete surgery including those with initiated chemotherapy at an outside institution were included. Surgical results, morbidity and prognosis were evaluated in patients with immediate re-operation before chemotherapy and those with interval debulking. RESULTS: 48 eligible patients were identified in our tumor registry. Self-referral by patient was the most frequent mode of admission (n=21, 43.8%). 22 patients (45.8%) underwent immediate re-surgery and 26 patients (54.2%) had an interval debulking after chemotherapy. In 12 patients (54.5%), macroscopically complete tumor removal could be achieved by immediate re-operation and in 17 patients (65.4%) after chemotherapy. Major complications were observed more frequently in patients with interval debulking (26.9 vs. 9.1%, p=0.324). Median overall survival time was 53 and 34 months (p=0.110) after immediate and delayed re-operation, respectively. CONCLUSIONS: Upfront re-operation before start of chemotherapy is feasible and successful in an expertise referral center in more than half of patients with incomplete primary surgery elsewhere. Complete resection even after initial incomplete debulking could improve outcome. Therefore, referral to expertise centers in those patients should be considered. Progression-free survival and overall survival showed a non-significant trend and complication rate is a remarkable advantage in favor of upfront re-operation.

Tumor cell identification and classification in esophageal adenocarcinoma specimens by hyperspectral imaging.

Esophageal cancer is the sixth leading cause of cancer-related death worldwide. Histopathological confirmation is a key step in tumor diagnosis. Therefore, simplification in decision-making by discrimination between malignant and non-malignant cells of histological specimens can be provided by combination of new imaging technology and artificial intelligence (AI). In this work, hyperspectral imaging (HSI) data from 95 patients were used to classify three different histopathological features (squamous epithelium cells, esophageal adenocarcinoma (EAC) cells, and tumor stroma cells), based on a multi-layer perceptron with two hidden layers. We achieved an accuracy of 78% for EAC and stroma cells, and 80% for squamous epithelium. HSI combined with machine learning algorithms is a promising and innovative technique, which allows image acquisition beyond Red-Green-Blue (RGB) images. Further method validation and standardization will be necessary, before automated tumor cell identification algorithms can be used in daily clinical practice.

Impact of a structured quality management program on surgical outcome in primary advanced ovarian cancer.

OBJECTIVE: Surgical outcome in advanced ovarian cancer (AOC) is an important prognostic factor and the only factor amendable to improvement by optimization. Therefore, introduction of quality management programs (QM) regarding the surgical therapy in ovarian cancer may help to improve outcome. METHODS: We introduced a specific ovarian cancer quality management program in 2001 in our gynecologic oncology center. Analysis of 396 consecutive patients with primary surgery for advanced ovarian cancer FIGO stages IIB-IV operated before the introduction of the quality management program 1997-2000, or during the introduction years 2001-2003, or after establishing 2004-2008. RESULTS: Thirty-three percent had complete debulking to no macroscopic residual disease from 1997 to 2000. This rate increased to 47% in 2001-2003 (n = 86) and 62% in 2004-2008 (n = 259). The utilization of extended surgical procedures increased over time. Patients with complete resection had 5-YSR of 55% compared to 16% in patients with residuals 1-10 mm, and 13% in patients with residuals >1 cm (p < 0.001). The median OS increased from 26 months 1997-2000 to 37 months 2001-2003 and 45 months in 2004-2008 (p < 0.003). CONCLUSIONS: Optimizing surgical skills, infrastructure, and introduction of quality management programs may improve both surgical and overall outcome in advanced ovarian cancer.

[Surgical treatment of esophageal cancer-Indicators for quality in diagnostics and treatment]. / Chirurgische Therapie des Ösophaguskarzinoms ­ Qualitätsindikatoren für Diagnostik und Therapie.

BACKGROUND: Within the framework of the quality initiative of the German Society for General and Visceral Surgery (DGAV) a review article was compiled based on a systematic literature search. Recommendations for the current diagnostics and treatment of esophageal cancer were also elaborated. METHODS: The systematic literature search was carried out in March 2019 according to the PRISMA criteria using the MEDLINE databank. The recommendations were formulated based on a consensus in the DGAV. RESULTS AND CONCLUSION: Operations below the currently valid minimum quantity threshold should no longer be carried out. There are many indications that the minimum quantity in Germany should be raised to ≥20 resections/year/hospital in order to comprehensively improve the quality. Prehabilitation programs with endurance, strength and intensive breathing training as well as nutritional therapy improve patient outcome. The current treatment of esophageal cancer is stage-dependent and incorporates endoscopic resection of (sub)mucosal low-risk tumors (T1m1-3 or T1sm1 low risk), primary esophagectomy of submucosal high-risk tumors (T1a), submucosal cancer (T1sm2-3) and T2N0 tumors, multimodal treatment with neoadjuvant chemoradiotherapy or perioperative chemotherapy and operations for advanced stages. Esophagectomy is nowadays carried out in one stage as a so-called hybrid procedure (laparoscopy and muscle-preserving thoracotomy) or as a total minimally invasive operation (laparoscopy and thoracoscopy).

Shared Genetic Etiology of Obesity-Related Traits and Barrett's Esophagus/Adenocarcinoma: Insights from Genome-Wide Association Studies.

BACKGROUND: Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits. METHODS: Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. For single marker analyses, all genome-wide significant risk alleles for BMI and WHR were compared with summary statistics of the BE/EA meta-analyses. RESULTS: Sex-combined analyses revealed a significant genetic correlation between BMI and BE/EA (rg = 0.13, P = 2 × 10-04) and a rg of 0.12 between WHR and BE/EA (P = 1 × 10-02). Sex-specific analyses revealed a pronounced genetic correlation between BMI and EA in females (rg = 0.17, P = 1.2 × 10-03), and WHR and EA in males (rg = 0.18, P = 1.51 × 10-02). On the single marker level, significant enrichment of concordant effects was observed for BMI and BE/EA risk variants (P = 8.45 × 10-03) and WHR and BE/EA risk variants (P = 2 × 10-02). CONCLUSIONS: Our study provides evidence for sex-specific genetic correlations that might reflect specific biological mecha-nisms. The data demonstrate that shared genetic factors are particularly relevant in progression from BE to EA. IMPACT: Our study quantifies the genetic correlation between BE/EA and obesity. Further research is now warranted to elucidate these effects and to understand the shared pathophysiology.