Impact of the introduction of an enhanced recovery pathway in esophageal cancer surgery: a cohort study and propensity score matching analysis.

Enhanced recovery pathways (ERP) have the potential to improve clinical outcomes. Aim of this study was to determine the impact of ERP on perioperative results as compared with traditional care (TC) after esophagectomy. In this study, two cohorts were compared. Cohort 1 represented 296 patients to whom TC was provided. Cohort 2 consisted of 200 unselected ERP patients. Primary endpoints were postoperative complications. Secondary endpoints were the length of stay and 30-day readmission rates. To confirm the possible impact of ERP, a propensity matched analysis (1:1) was conducted. A significant decrease in complications was found in ERP patients, especially for pneumonia and respiratory failure requiring reintubation (39% in TC and 14% in ERP; P<0.0001 and 17% vs. 12%; P<0.0001, respectively) and postoperative blood transfusion (26.7%-11%; P<0.0001). Furthermore, median length of stay was also significantly shorter: 13 days (interquartile range [IQR] 10-23) in TC compared with 10 days (IQR 8-14) in ERP patients (P<0.0001). The 30-day readmission rate (5.4% in TC and 9% in ERP; P=0.121) and in-hospital mortality rate (4.4% in TC and 2.5% in ERP; P=0.270) were not significantly affected. A propensity score matching confirmed a significant impact on pneumonia (P=0.0001), anastomotic leak (P=0.047), several infectious complications (P=0.01-0.034), blood transfusion (P=0.001), Comprehensive Complications Index (P=0.01), and length of stay (P=0.0001). We conclude that ERP for esophagectomy is associated with significantly fewer postoperative complications and blood transfusions, which results in a significant decrease of length of stay without affecting readmission and mortality rates.

Prognostic value of the circumferential resection margin and its definitions in esophageal cancer patients after neoadjuvant chemoradiotherapy.

The accepted importance of a positive circumferential resection margin (CRM) (defined as R1 in the TNM classification) is based on histopathology of the resection specimen obtained after primary surgery in esophageal cancer patients. The aim of this study is to look for the prognostic value of CRM after neoadjuvant chemoradiotherapy and to compare the clinical significance of a histologically CRM < 1 mm from the cut margin (Royal College of Pathologists definition of R1) to a positive cut margin (College of American Pathologists definition of R1) and to ≥1 mm margin (R0) resections in patients with ypT3-esophageal tumors after neoadjuvant chemoradiotherapy. Between 2000 and 2014, 458 patients who received esophagectomy after neoadjuvant chemoradiation therapy were selected. Overall (OS) and disease-free survival (DFS) were calculated by means of Kaplan-Meier curves and compared by Cox regression analysis. There were 163 (35.9%) patients who had a ypT3 tumor; in 118 (72.4%) resection was complete (R0). In 37 (22.7%) patients a CRM < 1 mm was found and 8 (4.9%) had a circumferential R1-resection. CRM involvement was inversely correlated with tumor regression grading, lymph node capsular involvement, and number of positive lymph nodes. On univariate analysis, no statistically significant difference was found between R0-resection and CRM < 1 mm (P = 0.103) for OS, but DFS showed a significant difference (P = 0.025). Circumferential R1-resections showed a significant difference compared to R0-resections for OS and DFS (both P = 0.002). In multivariate analysis, extracapsular lymph node involvement and circumferential R1-resection were withheld as independent prognosticators for OS, whereas extracapsular lymph node involvement, absence of regression on the primary tumor and circumferential R1-resection were withheld for DFS. After correcting for different variables in the multivariate model, CRM < 1 mm showed no statistical difference compared to R0-resections neither for OS nor for DFS. After neoadjuvant chemoradiotherapy, CRM is correlated with biological behavior of the tumor and with therapy response. Furthermore it is an independent prognosticator for OS and DFS. However CRM < 1 mm itself is no independent prognosticator for OS nor DFS survival in multivariable analysis. These results suggest that the definition of R1-resection should be limited to true invasion of the section plane.

Isolated local recurrence or solitary solid organ metastasis after esophagectomy for cancer is not the end of the road.

Recurrent disease after esophagectomy bears an infaust prognosis, especially when multiple recurrences are present. But little is known about survival in patients with limited recurrence (solitary locoregional recurrence or solid organ metastasis). Herein, we report our experience with these subgroups. We analyzed 1754 consecutive patients surgically treated with curative resection for esophageal cancer and cancer of the gastroesophageal junction between 1990 and 2012. Seven subgroups were defined according to the recurrence type (locoregional vs. organ metastasis), the site of recurrence (abdominal, thoracic, cervical for lymph nodes and lung, liver, adrenals and others for organ metastasis) and also the number of lesions (one vs. multiple lymph node stations or organ metastasis) Of these groups; clinical isolated locoregional recurrence (ciLR) was defined as solitary lymph-node recurrence confined to one compartment (cervical, thoracic or abdominal, within or outside surgical dissection-field) at clinical staging. Clinical solitary solid organ metastasis (csSOM) was defined as metastasis in a resectable solid organ, i.e. liver, lung, brain or adrenal. Salvage therapies were grouped in five categories. Kaplan-Meier curves were used to calculate survival. Recurrent disease was observed in 766 patients (43.7%) with overall 5-year survival of 4.5% after diagnosis of recurrence. Fifty-seven patients (7.4%) showed ciLR and 110 (14.4%) csSOM. Median time-to-recurrence was 16.8 months in ciLR and 9.9 months in csSOM (P = 0.0074). Survival is significantly improved compared to supportive therapy when local therapy is possible (P < 0.0001). In 25 (15%) of ciLR or csSOM patients, surgical therapy with or without systemic therapy, yielded a 5-year survival of 49.9% (median 54.8 months) after diagnosis of recurrence. When surgery was impossible or contraindicated, the combination of chemoradiotherapy appeared to be superior to chemotherapy alone (respectively 27.0% vs. 4.6% 5-year survival) or radiotherapy alone (no 5-year survival). Recurrent disease after esophagectomy is a common problem with poor overall survival. However prolonged survival could be obtained in selected patients if the recurrent disease is limited to ciLR or csSOM, if surgery (+/- systemic therapy) can be performed. If not a combination of chemoradiotherapy seems to offer the second best option. Patients presenting with a ciLR or csSOM should be discussed in a dedicated multidisciplinary team meeting as to evaluate and define the place of salvage treatment which in well selected cases could offer a perspective of prolonged survival.

Worldwide Esophageal Cancer Collaboration: pathologic staging data.

We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning.

Worldwide Esophageal Cancer Collaboration: clinical staging data.

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection.

Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data.

To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0-1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non-risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection.

Neoadjuvant chemoradiation treatment followed by surgery for esophageal cancer: there is much more than the mandard tumor regression score.

OBJECTIVE: Tumor regression grading (TRG) systems categorize residual tumor volume on the primary tumor after neoadjuvant treatment. Aim was to evaluate the impact of Mandard TRG, residual tumor depth (ypT) and residual lymph node status (ypN) and extent (ELNI) i.e. intracapsular versus extracapsular involvement on overall (OS) and disease-free survival (DFS) in esophageal carcinoma. METHODS: Between 2005 and 2014, 344 patients receiving R0-esophagectomy after neoadjuvant chemoradiation therapy (nCRT) were selected. Mandard TRG, ypTN and ELNI were prospectively recorded. RESULTS: Mandard TRG1 was found in 110 (32%); TRG2 in 120 (35%); TRG3 in 53 (15%); TRG4 in 54 (16%) and TRG5 in 7 (2%) patients. Both OS and DFS showed no significant difference between TRG1 and 2 (p = 0.059 and 0.105, respectively). Therefore, TRG1/2 was classified together as 'major response', TRG3/4 as 'minor response' and TRG5 as 'no response'. Multivariate analysis showed two independent prognosticators for OS (tumor regression response (TRR) and number of positive lymph nodes) and three independent prognosticators for DFS (TRR, ypT and ELNI). CONCLUSION: After nCRT followed by surgery for esophageal carcinoma, number of residual positive lymph nodes as well as TRR are prognosticators for OS. Minor TRR, ypT and extracapsular lymph node invasion are prognosticators for recurrence.

Quality indicators for oesophageal and gastric cancer: a population-based study in Belgium, 2004-2008.

This study aimed at developing and measuring quality indicators for oesophageal cancer (OC) and gastric cancer (GC) and to support quality improvement for practitioners. Quality indicators were identified from a systematic literature search including clinical guidelines. The selection process involved experts evaluating relevance, reliability, interpretability and actionability of each indicator. Three national databases were linked: the cancer registry, the population registry and the claims database. Completeness and validity of the data were validated before being measured for 10,660 patients diagnosed between 2004 and 2008. From a final set of 29 indicators, 18 were measurable using the available data. In 2008, less than 50% of patients were discussed at a multidisciplinary team meeting and less than 90% underwent a computed tomography scan 1 month after incidence date for cancer staging. Five-year relative survival was 22% for OC and 34.3% for GC. The post-operative mortality in OC patients was 4.8% (30 days) and 9.9% (90 days), whereas it reached 5.6 and 12.0% respectively in GC patients. This study demonstrates the feasibility to develop a set of quality indicators for gastro-oesophageal cancer. A mixed picture of the quality of care was illustrated for some relevant care processes. Nevertheless, 5-year survival is higher than reported in neighbouring countries.

Recurrence pattern in patients with a pathologically complete response after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer.

BACKGROUND: Little is known about recurrence patterns in patients with a pathologically complete response (pCR) or an incomplete response after neoadjuvant chemoradiotherapy (CRT) followed by resection for oesophageal cancer. This study was performed to determine the pattern of recurrence in patients with a pCR after neoadjuvant CRT followed by surgery. METHODS: All patients who received neoadjuvant CRT followed by oesophagectomy between 1993 and 2009 were identified from a database, and categorized according to pathological tumour response. Recurrences were classified as locoregional or distant. RESULTS: One hundred and eighty-eight patients were included. Median potential follow-up was 71·6 months. A pCR was achieved in 62 (33·0 per cent) of 188 patients. Recurrence developed in 24 (39 per cent) of 62 patients with a pCR and 70 (55·6 per cent) of 126 without a pCR (P = 0·044). Locoregional recurrence with or without synchronous distant metastases occurred in eight patients (13 per cent) in the pCR group and 31 (24·6 per cent) in the non-pCR group (P = 0·095). Locoregional recurrences without synchronous distant metastases occurred four (6 per cent) and ten (7·9 per cent) patients respectively (P = 0·945). The overall 5-year survival rate was significantly higher in the pCR group than in the non-pCR group (52 versus 33·9 per cent respectively; P = 0·019). CONCLUSION: Of patients with a pCR, 13 per cent still developed a locoregional recurrence. Although pCR is more favourable for survival, it is not synonymous with cure or complete locoregional disease control.

Spontaneous haemopneumothorax.

Spontaneous haemopneumothorax (SHP) is a rare, potential life-threatening emergency. Patients suffering from spontaneous haemopneumothorax can present at the emergency department with dyspnoea and unexplained signs of significant hypovolemia. Discussion about patient selection, timing and technique of operation is still alive. Standard chest roentgenogram is the most useful way to diagnose spontaneous haemopneumothorax, although false negative results exist. In most cases, initial conservative treatment requires later surgical intervention. So early surgical management is needed. In haemodynamic stable patients without any contra-indications, VATS is the preferred treatment method. However there's still discussion about the timing of surgery in hemodynamically instable patients.

A multicenter study of survival after neoadjuvant radiotherapy/chemotherapy and esophagectomy for ypT0N0M0R0 esophageal cancer.

OBJECTIVE: To evaluate 5-year survival of patients with locally advanced esophageal cancer (LAEC) who have undergone multimodality treatment with complete histopathologic response. BACKGROUND: Patients with LAEC may obtain excellent local-regional response to multimodality therapy. The overall benefit of a complete histopathologic response, when no viable tumor is present in the surgical specimen, is incompletely understood and existing data are limited to single-center studies with relatively few patients. The aim of this multicenter study was to define the outcome of patients with complete histopathologic response after multimodality therapy for LAEC. METHODS: The study population included 299 patients (229 male, 70 female; median age: 60 years) with LAEC (cT2N1M0, T3-4N0-1M0; 181 adenocarcinomas, 118 squamous carcinomas) who underwent either neoadjuvant radiochemotherapy (n = 284) or chemotherapy (n = 15) followed by esophagectomy at 6 specialized centers: Europe (3) and United States (3). All patients in the study had stage ypT0N0M0R0 after resection. RESULTS: Esophagectomy with thoracotomy (n = 255) was more frequent than with a transhiatal approach (n = 44). The median number of analyzed lymph nodes in the surgical specimens was 20 (minimum-maximum: 1-77). Thirty-day mortality rate was 2.4% and 90-day mortality rate was 5.7%. Overall 5-year survival rate was 55%. The disease-specific 5-year survival rate was 68%, with a recurrence rate of 23.4% (n = 70; local vs distant recurrence: 3.3% vs 20.1%). Cox regression analysis identified age as the only independent predictor of survival, whereas gender, histology, type of esophagectomy, type of neoadjuvant therapy, and the number of resected lymph nodes had no prognostic impact. CONCLUSION: Patients with histopathologic complete response at the time of resection of LAEC achieve excellent survival.

Surgical management of submucosal esophageal cancer: extended or regional lymphadenectomy?

INTRODUCTION: Radical esophagectomy is considered the standard therapy for tumors that infiltrate the submucosa of the esophagus (T1b), as the prevalence of lymph node metastases has been reported in up to 40% of these patients. It remains unclear whether radical esophagectomy with extended lymphadenectomy is needed or whether a surgical procedure with only regional lymphadenectomy suffices. The aim of this study was to compare outcomes of patients who underwent esophagectomy for T1b cancer through a transthoracic approach with extended lymphadenectomy (TTE) with those of patients in whom transhiatal esophagectomy (THE) was performed with a regional lymph node dissection. METHODS: Patients who underwent esophagectomy for T1b cancer between 1990 and 2004 and who did not receive (neo)adjuvant therapy were included. Data were collected from prospective databases of 4 centers. In Leuven, Belgium (n = 101), and Los Angeles, CA (n = 31), patients with T1b tumors had been operated on via TTE with extended lymphadenectomy, whereas in Amsterdam (n = 43) and Rotterdam (n = 47), the Netherlands, THE with regional lymphadenectomy had been performed. RESULTS: The 2 patient groups (TTE, n = 132; THE, n = 90) were comparable with regard to age, body mass index, and ASA classification. Operative time was longer in patients who underwent TTE (390 minutes) versus THE (250 minutes) (P < 0.001). The yield of lymph nodes resected was higher in the TTE group (median: 32) versus THE (median: 10) (P < 0.001). Overall morbidity, in-hospital mortality, and length of hospital stay were comparable between both the groups. In the TTE group, 27.3% of complications were classified as major versus 14.4% in the THE group (P < 0.001); however, the reoperation rate was higher after THE (12.2%) versus TTE (3.8%) (P = 0.01). There was no difference in pathological outcomes (infiltration depth, pN stage, pM stage, positive lymph node ratio) between both groups. Overall, 5-year survival (63.4% TTE vs 69.4% THE; P = 0.55) and disease-free 5-year survival (76.9% TTE vs 78.3% THE; P = 0.65) were comparable between both the groups. In patients with N1 disease, disease-free 5-year survival was 49.8% in the TTE group versus 40.0% in the THE group (P = 0.57). CONCLUSIONS: In patients with submucosal esophageal cancer (T1b), TTE with extended lymphadenectomy and THE with regional lymphadenectomy had similar short-term outcome and long-term survival. In the selected group of T1bN1 patients, TTE may be the preferred operative technique because of a potential disease-free survival benefit; in patients with T1bN0 disease, THE with en bloc dissection of the esophagus and regional lymph nodes offers an oncologically safe and less invasive treatment.

Cervical videomediastinoscopy.

Cervical mediastinoscopy is a frequently used technique to assess the mediastinum, in particular the mediastinal lymph nodes in patients presenting with non-small cell lung cancer (NSCLC). The senior author of this article is credited for developing in 1989 the concept of what is now called videomediastinoscopy. The introduction of videomediastinoscopy has proven to be superior to conventional mediastinoscopy and has made teaching of this operation much easier. However, imaging modalities, in particular positron emission tomography, have substantially decreased the need for mediastinoscopy in early stage NSCLC, while in more advanced stages the indication for primary staging and/or restaging after induction therapy is now challenged by the increasing experience with endobronchial ultrasound, endoesophageal ultrasound, and fine-needle aspiration. This article discusses the current deployment of videomediastinoscopy in the diagnosis and management of NSCLC.

Worldwide esophageal cancer collaboration.

The aim of this study is to report assemblage of a large multi-institutional international database of esophageal cancer patients, patient and tumor characteristics, and survival of patients undergoing esophagectomy alone and its correlates. Forty-eight institutions were approached and agreed to participate in a worldwide esophageal cancer collaboration (WECC), and 13 (Asia, 2; Europe, 2; North America, 9) submitted data as of July 1, 2007. These were used to construct a de-identified database of 7884 esophageal cancer patients who underwent esophagectomy. Four thousand six hundred and twenty-seven esophagectomy patients had no induction or adjuvant therapy. Mean age was 62 +/- 11 years, 77% were men, and 33% were Asian. Mean tumor length was 3.3 +/- 2.5 cm, and esophageal location was upper in 4.1%, middle in 27%, and lower in 69%. Histopathologic cell type was adenocarcinoma in 60% and squamous cell in 40%. Histologic grade was G1 in 32%, G2 in 33%, G3 in 35%, and G4 in 0.18%. pT classification was pTis in 7.3%, pT1 in 23%, pT2 in 16%, pT3 in 51%, and pT4 in 3.3%. pN classification was pN0 in 56% and pN1 in 44%. The number of lymph nodes positive for cancer was 1 in 12%, 2 in 8%, 3 in 5%, and >3 in 18%. Resection was R0 in 87%, R1 in 11%, and R2 in 3%. Overall survival was 78, 42, and 31% at 1, 5, and 10 years, respectively. Unlike single-institution studies, in this worldwide collaboration, survival progressively decreases and is distinctively stratified by all variables except region of the world. A worldwide esophageal cancer database has been assembled that overcomes problems of rarity of this cancer. It reveals that survival progressively (monotonically) decreased and was distinctively stratified by all variables except region of the world. Thus, it forms the basis for data-driven esophageal cancer staging. More centers are needed and encouraged to join WECC.

Morbidity and mortality after induction chemotherapy followed by surgery in IIIa-N2 non small cell lung cancer.

OBJECTIVE: To evaluate the frequency and risk of postoperative complications and mortality in patients with IIIa-N2 non small cell lung cancer after induction chemotherapy and surgery. METHODS: In a surgical database records from ninety two patients, operated between January 1, 2000 and December 31, 2006 were reviewed. Univariate analysis was used to identify predictors of postoperative complications and in-hospital mortality. RESULTS: All cases were histologically confirmed stage IIIa-N2. All patients received preoperative platinum based chemotherapy without radiotherapy. Pneumonectomy was performed in 20 cases (23.5%), from which 9 right sided. (Bi)lobectomy was performed in 53 cases (62.4%) and sleeve lobectomy in 11 cases (17.2%). One wedge resection was performed (1.2%). In 7 cases (7.6%) only an exploration was done. Complications developed in 35 patients (38%). Major complications in 15 patients (16%). No bronchopleural fistulae were observed. Analysis identified increased age and high physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) as a risk factor to develop complications, and a high simplified comorbidity score as a risk factor to develop a major complication. Higher age, Charlson comorbidity index, simplified comorbidity score and POSSUM were a risk factor for developing pneumonia. CONCLUSION: Although surgery after induction therapy for IIIa-N2 NSCLC can be done with a morbidity and mortality comparable to surgery alone, it remains a high risk operation. It should therefore be performed in a center with experience. Bronchial stump protection should be used whenever there is an increased risk for developing a bronchopleural fistula. In deciding whether to do surgery or radiotherapy one should keep in mind the feasibility of performing a complete resection together with a preoperative assessment to predict complications and mortality. For the preoperative assessment several scoring systems can be used from which we find the simplified comorbidity score most useful.

Multivariate analysis of the association of acid and duodeno-gastro-oesophageal reflux exposure with the presence of oesophagitis, the severity of oesophagitis and Barrett's oesophagus.

BACKGROUND: Exposure to acid and duodeno-gastro-oesophageal reflux (DGOR) both increase with oesophageal lesions in gastro-oesophageal reflux disease (GORD). It is unknown whether DGOR exposure is an independent risk factor for oesophageal lesions. A multivariate analysis was performed on the relationship between oesophageal lesions and demographics and acid and DGOR exposure. METHODS: In 422 patients with suspected GORD, upper endoscopy, oesophageal manometry, and pH and DGOR monitoring were performed. Stepwise logistic regression was used to identify factors associated with the presence of oesophagitis, severity of oesophagitis and the presence of Barrett's oesophagus. ORs and 95% CIs were computed at different cut-offs. RESULTS: 54% of the patients had no oesophagitis, 36% had grade A-B oesophagitis, 3% had grade C-D oesophagitis and 7% had Barrett's oesophagus. In multivariate analysis, oesophagitis was associated with hiatal hernia (OR 3.621, 95% CI 2.263 to 5.794) and DGOR exposure (OR up to 2.236, 95% CI 1.356-3.685), while a low body mass index (BMI) seemed protective (OR for BMI >first quartile 2.245, 95% CI 1.371 to 3.677). Severity of oesophagitis was only associated with acid exposure (OR up to 5.038, 95% CI 1.452 to 17.480). The presence of Barrett's oesophagus was associated with male sex (OR 3.621, 95% CI 2.263 to 5.794), DGOR (OR up to 5.017, 95% CI 2.051 to 12.274) and acid exposure (OR up to 3.031, 95% CI 1.216 to 7.556). CONCLUSIONS: Several independent factors are associated with oesophageal lesions in GORD. The risk of oesophagitis is associated with hiatal hernia, BMI and DGOR exposure; severity of oesophagitis depends on acid exposure; and Barrett's oesophagus is associated with male sex and exposure to both acid and DGOR.

Predicting individual survival after potentially curative esophagectomy for adenocarcinoma of the esophagus or gastroesophageal junction.

INTRODUCTION: Even after potentially curative esophagectomy, the majority of patients with adenocarcinoma of the esophagus or gastroesophageal junction die due to cancer recurrence. To predict individual disease-specific survival, a nomogram has been developed in a high-volume center in the Netherlands. The validity of this nomogram was externally tested in patients treated in another country at a different high-volume institution. METHODS: Clinicopathological data from patients who underwent a macroscopically radical resection in a high-volume center in Leuven, Belgium, were used to validate the original nomogram based on a Cox regression model. Moreover, it was examined whether adjusting the value of the original coefficients of the predictors or adding new predictors would improve the fit of the nomogram in the validation cohort. Calibration was evaluated by comparing the observed survival with the expected survival as predicted by the original nomogram across patients with different risk profiles. The discriminatory ability of the nomogram was determined in the validation cohort, using the concordance index and compared with the original estimate. RESULTS: A total of 382 patients were used in the validation study. The median esophageal cancer-specific survival was 38 months. None of the coefficients re-estimated in the validation cohort differed significantly from the values of the original nomogram. Observed and expected survival curves showed good calibration. Discrimination of the original nomogram was preserved in the validation cohort: the concordance index hardly decreased from 0.77 in the original cohort to 0.76 in the validation cohort. CONCLUSIONS: The nomogram model that was originally developed in a Dutch institute had good individual discriminatory properties and good overall calibration when applied to an independent series of patients. The nomogram was updated using the data from both cohorts to provide even more robust estimates of survival for individual patients. This tool is clinically helpful to supply more reliable prognostic information, to offer tailored follow-up schedules and/or novel therapeutic strategies in subgroups of patients with higher risk of recurrence.

The lectin-like domain of thrombomodulin protects against ischaemia-reperfusion lung injury.

Ischaemia-reperfusion injury of the lung is a major cause of morbidity and mortality, particularly following lung transplantation, the mainstay treatment for patients with end-stage pulmonary disease. Effective measures to prevent this complication are lacking. Thrombomodulin (TM) is an endothelial cell receptor and cofactor for thrombin-mediated generation of the anticoagulant and anti-inflammatory activated protein C (APC). The N-terminal lectin-like domain (LLD) of TM has no direct effects on coagulation, but has distinct anti-inflammatory properties, interfering with leukocyte adhesion, complement activation and cytokine generation, all of which are hallmarks of ischaemia-reperfusion injury. Using a murine model of lung ischaemia-reperfusion injury (90 min ischaemia, 4 h reperfusion), the present study shows that mice lacking the LLD of TM respond with increased extravasation of neutrophils and macrophages into the lung parenchyma and bronchoalveolar fluid (BALF), with augmented BALF levels of cytokines interleukin (IL)-1beta and granulocyte-monocytic colony-stimulating factor (GM-CSF). Pre-treatment of wild-type mice with recombinant LLD, as compared with controls, significantly suppresses protein leakage and accumulation of leukocytes in the BALF. These novel findings support further evaluation of recombinant lectin-like domain of thrombomodulin to protect the lung against tissue-damaging pro-inflammatory responses following ischaemia-reperfusion.

The importance of lymphocytes in lung ischemia-reperfusion injury.

In a murine model of lung ischemia-reperfusion injury (IRI), we previously demonstrated that lymphocytes increase in the alveolar space during the ischemic period. We hypothesized that these lymphocytes play an important role during ischemia in the development of lung IRI. In the present study, severe combined immunodeficiency (SCID) mice, lacking T cells, were used to further investigate our hypothesis. SCID and control mice underwent 90 minutes of left lung ischemia followed by 4 hours of reperfusion. A significant decrease in neutrophils, together with lower levels of interleukin-1beta, was found in SCID mice after reperfusion. We concluded that lymphocytes invading the lung during ischemia trigger an inflammatory response upon reperfusion. Antilymphocyte therapies in the donor should be further investigated as treatment strategies against IRI.

Modification of the arterial anastomotic technique improves survival in porcine single lung transplant model.

BACKGROUND: Lung transplantation is a valuable therapeutic option for selected patients with end-stage pulmonary disease. However, this treatment is complicated by ischaemia-reperfusion injury (IRI) of the lung in 10-20% of the recipients. We developed an unilateral porcine lung transplant model to study IRI and describe our experience with two different arterial anastomotic techniques. MATERIAL & METHODS: Twenty four domestic pigs [n = 6 x (donor + recipient)/group] were used in this study. Donor lungs were harvested using an antegrade flush with cold Perfadex and stored in the same solution for +/- 8 hours. Recipient animals underwent a left thoracotomy. After native pneumonectomy, the left donor lung was transplanted in the following order: 1. left atrial cuff; 2. bronchus; 3 pulmonary artery. 2 The outcome in recipients from historical groups differing in anastomotic technique was compared. An end-to-end anastomosis on the left pulmonary artery was performed in group I versus a patch anastomosis on the main pulmonary artery in group II. One hour after reperfusion, the right pulmonary artery and main bronchus were ligated forcing the recipient to survive on the transplanted lung only. The animals were further observed for 6 hours. RESULTS: Survival 6 hours after exclusion of the right lung was 33% (2/6) in group I versus 83% (5/6) in group II. Animals in group I died of right heart failure manifested by acute dilation of the right ventricle following ligation of the hilum of the right lung. CONCLUSION: Single lung transplantation with exclusion of the contralateral native lung is a critical model. Arterial end-to-end anastomosis resulted in an increased right ventricular afterload. The use of a patch technique improved the compliance of the arterial anastomosis and decreased early mortality. This transplant model is currently used in our laboratory to assess new methods for pulmonary preservation.