Deficient mismatch repair screening of advanced adenomas in the population screening program for colorectal cancer is not effective.

AIM: Currently, screening of colorectal cancers (CRC) by assessing mismatch repair deficiency (dMMR) or microsatellite instability (MSI) is used to identify Lynch syndrome (LS) patients. Advanced adenomas are considered immediate precursor lesions of CRC. In this study we investigate the relevance of screening of advanced adenomas for LS in population screening. METHODS AND RESULTS: Advanced adenomas (n = 1572) were selected from the Dutch colorectal cancer population screening programme, based on one or more of the criteria: tubulovillous (n = 848, 54%) or villous adenoma (n = 118, 7.5%), diameter ≥ 1 cm (n = 1286, 82%) and/or high-grade dysplasia (n = 176, 11%). In 86 cases (5%), all three criteria were fulfilled at the same time. MMR-IHC and/or MSI analyses were performed on all cases. Only five advanced adenomas (0.3%) showed dMMR and MSI, including two cases with hypermethylation. In at least two patients a germline event was suspected based on allelic frequencies. No pathogenic explanation was found in the last case. CONCLUSION: Timely testing of precursor lesions would be preferable to detect new LS patients before CRC development. However, standard assessment of dMMR of advanced adenomas from the population screening is not effective.

Risk factors for advanced colorectal neoplasia and colorectal cancer detected at surveillance: a nationwide study in the modern era.

AIM: Recommendations for surveillance after colonoscopy are based on risk factors for metachronous advanced colorectal neoplasia (AN) and colorectal cancer (CRC). The value of these risk factors remains unclear in populations enriched by individuals with a positive faecal immunochemical test and were investigated in a modern setting. METHODS AND RESULTS: This population-based cohort study included all individuals in the Netherlands of ≥55 years old with a first adenoma diagnosis in 2015. A total of 22,471 patients were included. Data were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were metachronous AN and CRC. Patient and polyp characteristics were evaluated by multivariable Cox regression analyses. During follow-up, 2416 (10.8%) patients were diagnosed with AN, of which 557 (2.5% from the total population) were CRC. Adenomas with high-grade dysplasia (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.40-1.83), villous histology (HR 1.91, 95% CI 1.59-2.28), size ≥10 mm (HR 1.12, 95% CI 1.02-1.23), proximal location (HR 1.12, 95% CI 1.02-1.23), two or more adenomas (HR 1.28, 95% CI 1.16-1.41), and serrated polyps ≥10 mm (HR 1.67, 95% CI 1.42-1.97) were independent risk factors for metachronous AN. In contrast, only adenomas with high-grade dysplasia (HR 2.49, 95% CI 1.92-3.24) were an independent risk factor for metachronous CRC. CONCLUSIONS: Risk factors for metachronous AN and CRC were identified for populations with access to a faecal immunochemical test (FIT)-based screening programme. If only risk factors for metachronous CRC are considered, a reduction in criteria for surveillance seems reasonable.

Is There an Optimal Definition for a Positive Circumferential Resection Margin in Locally Advanced Esophageal Cancer?

BACKGROUND: Two definitions of a positive circumferential resection margin (CRM) in esophageal cancer coexist: one by the College of American Pathologists (CAP) (CRM = 0 mm) and another by the Royal College of Pathologists (RCP) (CRM ≤ 1 mm). This study aimed to evaluate the prognostic value of both definitions in esophageal cancer and to identify a new cutoff value for the CRM to predict survival. METHODS: Patients who underwent curative esophageal resection for locally advanced (≥ pT3) adenocarcinoma or squamous cell carcinoma were selected from 2007 to 2016. The CRM was reassessed using an ocular micrometer. Overall survival (OS) and disease-free survival were estimated with uni- and multivariate analyses. RESULTS: The study enrolled 283 patients: 48 with a positive CRM according to the CAP definition and 171 with a positive CRM according to the RCP definition. In the multivariate analysis, a positive CRM according to both definitions was significantly associated with a poor OS (CAP: hazard ratio [HR], 2.26, p < 0.001; RCP: HR, 1.42, p = 0.035). A CRM of 0 mm was predictive of a worse OS and DFS than a CRM of 1 mm or less (p < 0.0001), whereas no significant difference was found between a CRM greater than 1 mm and a CRM of 1 mm or less, indicating that the CAP definition was more accurate for predicting prognosis and recurrence. New cutoff CRM values of 100 µm in squamous cell carcinoma and 200 µm in adenocarcinoma were optimal for predicting OS. CONCLUSION: The CAP definition was more accurate for predicting prognosis and recurrence. The study identified a new cutoff value of CRM according to histologic type.

Patient-reported outcomes after oesophagectomy in the multicentre LASER study.

BACKGROUND: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. METHODS: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. RESULTS: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. CONCLUSION: A long-term symptom burden is common after oesophageal cancer surgery.

Correction to: Consensus on the pathological definition and classification of poorly cohesive gastric carcinoma.

The authors would like to correct the error in the publication of the original article. The surname and given names of the authors were swapped in the "Acknowledgements". The corrected detail is given below.

Consensus on the pathological definition and classification of poorly cohesive gastric carcinoma.

BACKGROUND AND AIMS: Clinicopathological characteristics of gastric cancer (GC) are changing, especially in the West with a decreasing incidence of distal, intestinal-type tumours and the corresponding increasing proportion of tumours with Laurén diffuse or WHO poorly cohesive (PC) including signet ring cell (SRC) histology. To accurately assess the behaviour and the prognosis of these GC subtypes, the standardization of pathological definitions is needed. METHODS: A multidisciplinary expert team belonging to the European Chapter of International Gastric Cancer Association (IGCA) identified 11 topics on pathological classifications used for PC and SRC GC. The topics were debated during a dedicated Workshop held in Verona in March 2017. Then, through a Delphi method, consensus statements for each topic were elaborated. RESULTS: A consensus was reached on the need to classify gastric carcinoma according to the most recent edition of the WHO classification which is currently WHO 2010. Moreover, to standardize the definition of SRC carcinomas, the proposal that only WHO PC carcinomas with more than 90% poorly cohesive cells having signet ring cell morphology have to be classified as SRC carcinomas was made. All other PC non-SRC types have to be further subdivided into PC carcinomas with SRC component (< 90% but > 10% SRCs) and PC carcinomas not otherwise specified (< 10% SRCs). CONCLUSION: The reported statements clarify some debated topics on pathological classifications used for PC and SRC GC. As such, this consensus classification would allow the generation of evidence on biological and prognostic differences between these GC subtypes.

Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08).

Background: This open-label, phase III trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients and methods: Patients were randomly assigned (1 : 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary end point was progression-free survival (PFS). Results: In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5-2.8) with control [hazard ratio (HR), 0.79; 95% CI, 0.58-1.07; P = 0.13]. Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2-4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52-1.01; P = 0.055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31-0.90; P = 0.017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64-1.59, P = 0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Conclusion: Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. Clinical trial information: NCT01107639.

A structured training program for minimally invasive esophagectomy for esophageal cancer- a Delphi consensus study in Europe.

Evidence suggests that structured training programs for laparoscopic procedures can ensure a safe standard of skill acquisition prior to independent practice. Although minimally invasive esophagectomy (MIO) is technically demanding, no consensus on requirements for training for the MIO procedure exists. The aim of this study is to determine essential steps required for a structured training program in MIO using the Delphi consensus methodology. Eighteen MIO experts from 13 European hospitals were asked to participate in this study. The consensus process consisted of two structured meetings with the expert panel, and two Delphi questionnaire rounds. A list of items required for training MIO were constructed for three key domains of MIO, including (1) requisite criteria for units wishing to be trained and (2) to proctor MIO, and (3) a framework of a MIO training program. Items were rated by the experts on a scale 1-5, where 1 signified 'not important' and 5 represented 'very important.' Consensus for each domain was defined as achieving Cronbach alpha ≥0.70. Items were considered as fundamental when ≥75% of experts rated it important (4) or very important (5). Both Delphi rounds were completed by 16 (89%) of the 18 invited experts, with a median experience of 18 years with minimally invasive surgery. Consensus was achieved for all three key domains. Following two rounds of a 107-item questionnaire, 50 items were rated as essential for training MIO. A consensus among European MIO experts on essential items required for training MIO is presented. The identified items can serve as directive principles and core standards for creating a comprehensive training program for MIO.

Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease.

Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by establishing a Lynch syndrome cohort from the Radboud University Medical Center (Nijmegen, The Netherlands) and the Academic Medical Center (Amsterdam, The Netherlands). Patients with heterozygous germline mutations in MLH1, MSH2 (and EPCAM deletion-mediated MSH2 methylation), MSH6, or PMS2 who were tested and/or treated from 1998 through 2014 were included. Patients who developed IBD were identified by linkage of this cohort to the Dutch nationwide Pathology Registry (PALGA). Subsequently, we compared the risk of CRC between Lynch syndrome patients with IBD and without IBD. Of 1046 patients with Lynch syndrome, 15 developed IBD (1.4%). Patients with Lynch syndrome and IBD were significantly younger (median age, 38.0 y) than patients with Lynch syndrome without IBD (median age, 52.0 y; P = .001). Nevertheless, a similar proportion of patients in each group developed CRC: 4 of the 15 patients (26.7%) with Lynch syndrome and IBD compared with 311 of the 1031 patients (30.2%) with Lynch syndrome without IBD. Patients with Lynch syndrome and IBD developed CRC at a younger age (median age, 36.0 y) than patients with Lynch syndrome without IBD (median age, 46.0 y; P = .045). However, the cumulative incidence of CRC was similar between groups (P = .121). All patients with Lynch syndrome and IBD who developed CRC had ulcerative colitis, producing a higher cumulative incidence of CRC for this IBD subgroup (P < .001). In conclusion, patients with Lynch syndrome and IBD develop CRC risk at a younger age than patients without IBD; patients with ulcerative colitis are at especially high risk.

ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS).

BACKGROUND: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. METHODS: This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. DISCUSSION: This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). TRIAL REGISTRATION: NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.

Same-day discharge in benign esophageal surgery: a prospective cohort study.

Day-case esophageal surgery has been demonstrated to be safe in small prospective cohorts and only for laparoscopic fundoplication. The aims of this study are to assess the feasibility and safety of a large series of esophageal day-case surgeries, including laparoscopic Nissen fundoplication (LNF), Zenker diverticulectomy (ZD), and laparoscopic Heller myotomy (LHM) and to compare the outcomes among three procedures.This was a prospective, observational study of selected patients who underwent day-case LNF, ZD, and LHM between 2003 and 2013. Postoperative outcomes, the patients' satisfaction, and functional results were evaluated with dedicated scores and compared.Of the 427 patients who underwent surgery for those indications during the study period, 168 (39.3%) eligible patients underwent day-case procedures (134 LNF, 14 LHM, and 20 ZD). The overnight unplanned admission rate was 16.2% and was similar among the groups (P = 0.681). Ten patients were readmitted during the first postoperative week because of dysphagia (n = 6, all in the LNF group), flu-like syndrome (n = 1), and secondary perforation (n = 3, all in the LHM group). The unplanned seven-day readmission rate was significantly higher in the LHM group than in the ZD and LNF groups (P = 0.042). The 30-day rates of unplanned readmission and consultation were 8.9% (P = 0.300) and 4.8%, respectively. At follow-up, 87.5% of the patients were satisfied with day-case treatment, and the functional results were good for 81.4% of the patients.Day-case esophageal surgery is feasible for LNF and seems to be feasible for ZD. Safety criteria have not yet been met for LHM, requiring further adaptations.

Multicentre study of neoadjuvant chemotherapy for stage I and II oesophageal cancer.

BACKGROUND: The benefit of neoadjuvant chemotherapy (NCT) for early-stage oesophageal cancer is unknown. The aim of this study was to assess whether NCT improves the outcome of patients with stage I or II disease. METHODS: Data were collected from 30 European centres from 2000 to 2010. Patients who received NCT for stage I or II oesophageal cancer were compared with patients who underwent primary surgery with regard to postoperative morbidity, mortality, and overall and disease-free survival. Propensity score matching was used to adjust for differences in baseline characteristics. RESULTS: Of 1173 patients recruited (181 NCT, 992 primary surgery), 651 (55·5 per cent) had clinical stage I disease and 522 (44·5 per cent) had stage II disease. Comparisons of the NCT and primary surgery groups in the matched population (181 patients in each group) revealed in-hospital mortality rates of 4·4 and 5·5 per cent respectively (P = 0·660), R0 resection rates of 91·7 and 86·7 per cent (P = 0·338), 5-year overall survival rates of 47·7 and 38·6 per cent (hazard ratio (HR) 0·68, 95 per cent c.i. 0·49 to 0·93; P = 0·016), and 5-year disease-free survival rates of 44·9 and 36·1 per cent (HR 0·68, 0·50 to 0·93; P = 0·017). CONCLUSION: NCT was associated with better overall and disease-free survival in patients with stage I or II oesophageal cancer, without increasing postoperative morbidity.

Patterns of recurrence in early-stage oesophageal cancer after chemoradiotherapy and surgery compared with surgery alone.

BACKGROUND: Patterns of disease recurrence in patients with oesophageal cancer following treatment with neoadjuvant chemoradiotherapy and surgery (nCRTS) or surgery alone are poorly reported. An understanding of patterns of disease recurrence is important for subsequent treatment planning. METHODS: An analysis was undertaken of patterns of disease recurrence from a phase III multicentre randomized trial (FFCD9901) comparing nCRTS with surgery alone in patients with stage I and II oesophageal cancer. RESULTS: Some 170 patients undergoing surgical resection were included in the study. R0 resection rates were similar in the two groups: 94 per cent following nCRTS versus 92 per cent after surgery alone (P = 0·749). After a median follow-up of 94·2 months, recurrent disease was found in 39·4 per cent of the overall cohort (31 per cent after nCRTS versus 47 per cent following surgery alone; P = 0·030). Locoregional recurrence was diagnosed in 41 patients (17 versus 30 per cent respectively; P = 0·047) and distant metastatic recurrence in 47 (23 versus 31 per cent respectively; P = 0·244). Metastatic recurrence was more frequent in patients with adenocarcinoma than in those with squamous cell cancer (40 versus 23·1 per cent respectively; P = 0·032). ypT0 N0 category was associated with prolonged time to mixed locoregional and metastatic recurrence (P = 0·009), and time to locoregional (P = 0·044) and metastatic (P = 0·055) recurrence. In multivariable analysis, node-positive disease predicted both locoregional (P = 0·001) and metastatic (P < 0·001) recurrence. CONCLUSION: Locoregional disease control following nCRTS indicated a local field effect not related solely to completeness of resection. pN+ disease was strongly predictive of time to locoregional and metastatic disease recurrence.

Consensus guidelines for enhanced recovery after gastrectomy: Enhanced Recovery After Surgery (ERAS®) Society recommendations.

BACKGROUND: Application of evidence-based perioperative care protocols reduces complication rates, accelerates recovery and shortens hospital stay. Presently, there are no comprehensive guidelines for perioperative care for gastrectomy. METHODS: An international working group within the Enhanced Recovery After Surgery (ERAS®) Society assembled an evidence-based comprehensive framework for optimal perioperative care for patients undergoing gastrectomy. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system and were discussed until consensus was reached within the group. The quality of evidence was rated 'high', 'moderate', 'low' or 'very low'. Recommendations were graded as 'strong' or 'weak'. RESULTS: The available evidence has been summarized and recommendations are given for 25 items, eight of which contain procedure-specific evidence. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations. CONCLUSION: The present evidence-based framework provides comprehensive advice on optimal perioperative care for the patient undergoing gastrectomy and facilitates multi-institutional prospective cohort registries and adequately powered randomized trials for further research.

Day-case versus inpatient laparoscopic fundoplication: outcomes, quality of life and cost-analysis.

BACKGROUND: Day-case laparoscopic Nissen-Rossetti fundoplication (LF) has been demonstrated to be safe in small, prospective cohorts. The purpose of the study was to compare postoperative course, functional results, quality of life, and healthcare costs in patients undergoing LF in a day-case surgical unit with same-day discharge and patients undergoing LF as an inpatient. METHODS: All consecutive patients in our department who underwent a primary LF for symptomatic uncomplicated gastroesophageal reflux disease from 2004 to 2011 were entered into a prospective database (n = 292). From 101 same-day discharge patients (day-case group), control inpatient procedures were randomly matched by age, gender, body mass index, American Society of Anesthesiologists classification, and presence of a hiatal hernia (inpatient group, n = 101). RESULTS: No postoperative deaths occurred and postoperative morbidity occurred in 9.4% of patients. When comparing day-case and inpatient groups, postoperative morbidity rates were 9.9 vs. 8.9% (p = 0.81) with median hospital stays and readmission rates of 1 vs. 4 days (p < 0.001) and 7.9 vs. 0% (p < 0.001), respectively. Gastrointestinal Quality of Life Index was significantly enhanced due to surgery (p < 0.001) and comparable in the two groups. Estimated direct healthcare costs per patient were 2,248 euros in the day-case group vs. 6,569 euros in the inpatient group (p < 0.001), equivalent to a cost saving of 3,921 euros. CONCLUSIONS: Day-case and inpatient approaches after LF give similar results in terms of postoperative mortality and morbidity, functional outcomes and quality of life, with a substantial cost saving in favor of a day-case procedure.

Isolated cerebellar metastasis from urothelial carcinoma: A case report of a rare phenomenon.

Introduction: Although urothelial carcinoma (UC) generally is non-invasive, contrastingly in 25% of patients UC metastasizes. Isolated central nervous system (CNS) metastasis from UC without other distant metastases are considered rare. In this report we describe a patient with an isolated and solitary cerebellar metastasis from UC. Research question: In this case report we explore the value of histological analysis of CNS metastases, imaging, treatment options and survival. Material and methods: A rare case is presented of a patient diagnosed with an isolated CNS metastasis originating from UC. Through a systematic review of literature route of dissemination, current imaging and treatment options, and survival are discussed. Results: A 77-year-old male was diagnosed with a pT2N0M0 high-grade UC and treated with transurethral resection and chemoradiation therapy. Several months later, the patient presented with neurological symptoms, and radiological imaging revealed a solitary cerebellar mass. A body CT scan showed no other metastasis. After surgical resection, histology confirmed urothelial origin of the mass, matching his primary UC and the patient received post-operative stereotactic radiotherapy at the surgical site. Recurrence of the cerebellar mass occurred after 6 months for which the patient received re-resection. The patient died 5.5 months after re-resection. Discussion and conclusion: Isolated brain metastases without other distant metastases from UC are rare, so histologic confirmation of the brain metastasis is essential, particularly when the time interval between diagnosis of the UC and brain metastasis increases. Early brain CT is not recommended. PET CT may have additional value in detection of other distant metastases from UC. Despite advancements in treatments, prognosis for CNS metastasis from UC remains poor.

Effects of hybrid minimally invasive oesophagectomy on major postoperative pulmonary complications.

BACKGROUND: Morbidity after oesophageal cancer surgery remains high, mainly due to major postoperative pulmonary complications (MPPCs). The aim of this study was to test the hypothesis that hybrid minimally invasive oesophagectomy (HMIO) decreases the 30-day MPPC rate without compromising oncological outcomes. METHODS: Consecutive patients undergoing curative oesophagectomy for cancer by laparoscopic gastric mobilization and open thoracotomy (HMIO) between January 2004 and December 2009 were matched to randomly selected patients undergoing a totally open approach during the same study interval. Matching variables were age, sex, cancer stage, location of the primary tumour, histological subtype, American Society of Anesthesiologists grade, malnutrition, neoadjuvant chemoradiation and epidural analgesia. RESULTS: MPPCs at 30 days were significantly less frequent after HMIO compared with open surgery (15·7 versus 42·9 per cent; P < 0·001). Postoperative in-hospital mortality and overall morbidity rates were 4·3 and 47·5 per cent respectively, again significantly lower in the HMIO group: 1·4 versus 7·1 per cent (P = 0·018) and 35·7 versus 59·3 per cent (P < 0·001). In multivariable analysis, HMIO, adenocarcinoma subtype, epidural analgesia and surgery after 2006 were independent protective factors against MPPCs, and HMIO was independently protective against acute respiratory distress syndrome (ARDS). Lymph node yields and survival were similar in the two groups. CONCLUSION: HMIO for oesophageal cancer, using laparoscopic gastric mobilization and open right thoracotomy, offered a substantial and independent protective effect against MPPCs, including ARDS, without compromising oncological outcomes.

Management of sporadic duodenal adenomas and the association with colorectal neoplasms: a retrospective cohort study.

GOALS: To evaluate management, outcome, and follow-up of patients with sporadic duodenal adenomas and assess the presence of colorectal neoplasms. BACKGROUND: With the widespread use of esophagogastroduodenoscopy, an increasing number of sporadic duodenal adenomas are diagnosed. An optimal algorithm for management has not been fully defined. Accumulating data suggest an association with colorectal neoplasms. STUDY: Patients diagnosed with sporadic duodenal adenomas at our institute from 1986 until 2008 were retrospectively reviewed. Data were collected from medical records. RESULTS: Fifty-four patients (28 men, 52%) were diagnosed with a sporadic duodenal adenoma at a median age of 59 years (range, 27 to 84 y); 33 patients (61%) underwent endoscopic or surgical intervention, 5 (9%) were only followed endoscopically, and 16 (30%) underwent no intervention or follow-up. Complete endoscopic removal was accomplished in at least 81% of cases, and no complications were reported; surgical intervention was complicated in 4 patients, with 1 resulting in death. Adenoma recurrence was 20% at a median follow-up of 18 months (range, 4 to 54 mo), but no carcinoma developed. Colorectal neoplasms were found in 16 of 29 patients (55%) who underwent colonoscopy, including 2 cancers (7%), 7 advanced adenomas (24%), and 7 nonadvanced adenomas (24%). CONCLUSIONS: Although no consistent approach to management of sporadic duodenal adenomas was followed, no duodenal carcinoma developed during the follow-up. Endoscopic intervention is preferred over surgical intervention, whenever possible. Once complete removal is ascertained, there is no strict indication for regular follow-up esophagogastroduodenoscopy, especially in elderly patients or patients with relevant comorbidity. Colonoscopic assessment is warranted in all patients diagnosed with sporadic duodenal adenomas.

A molecular "phase ordering" phase transition leading to a modulated aperiodic composite in n-heptane/urea.

n-Heptane/urea is an aperiodic inclusion compound in which the ratio of host and guest repeats along the channel axis is very close to unity and is found to have a constant value (0.981) from 280 K to 90 K. Below 280 K, two phase transitions are observed. The first (T(c1) = 145 K) is a ferroelastic phase transition that generates superstructure reflections for the host while leaving the guest with 1D order. The second (T(c2) = 130 K) is a "phase ordering" transition to a four-dimensional structure (P2(1)11(0ßγ)) with pronounced host-guest intermodulation and a temperature dependent phase shift between guests in adjacent channels.