Hans Van Veer

A decade of extended-criteria lung donors in a single center: was it justified?

Despite a worldwide need to expand the lung donor pool, approximately 75% of lung offers are not accepted for transplantation. We investigated the impact of liberalizing lung donor acceptance criteria during the last decade on the number of effective transplants and early and late outcomes in our center. All 514 consecutive lung transplants (LTx) performed between Jan 2000 and Oct 2011 were included. Donors were classified as matching standard criteria (SCD; n = 159) or extended criteria (ECD; n = 272) in case they fulfilled at least one of the following criteria: age >55 years, PaO2/FiO2 at PEEP 5 cmH2O < 300 mmHg at time of offer, presence of abnormalities on chest X‐ray, smoking history, presence of aspiration, presence of chest trauma, or donation after circulatory death. Outcome parameters were primary graft dysfunction (PGD) grade at 0, 12, 24, and 48 h after LTx, time to extubation, stay in intensive care unit (ICU), early and late infection, acute rejection and bronchiolitis obliterans syndrome (BOS), and survival. Two hundred and seventy‐two recipients (63.1%) received ECD lungs. PGD grade at T0 was similar between groups, while at T12 (<0.01), T24 (<0.01), and T48 (<0.05), PGD3 was observed more often in ECDs. ICU stay (P < 0.05) was longer in ECDs compared with SCDs. Time to extubation, respiratory infections, acute rejection, lymphocytic bronchiolitis, BOS, and survival were not different between groups. Accepting ECDs contributed in increasing the number of lung transplants performed in our center. Although this lung donor strategy has an impact on early postoperative outcome, liberalizing criteria did not influence long‐term outcome after LTx.

Signet Ring Cells in Esophageal and Gastroesophageal Junction Carcinomas Have a More Aggressive Biological Behavior

Objective:To clarify the biologic behavior of esophageal signet ring cell (SRC) carcinomas of the esophagus and gastroesophageal junction (GEJ). To evaluate the accuracy of pretreatment biopsies in diagnosing true SRC carcinoma. Background:In contrast with gastric cancer, little is known about the biologic behavior and prognosis of SRC. Methods:All adenocarcinomas (ADC) of the esophagus and GEJ-patients undergoing primary resection between 1990 and 2009 were included (n = 920). Specimens containing SRCs (n = 114) were classified according to World Health Organization criteria (>50% SRC or <50% SRC). Results:Thirty-two patients showed more than 50% SRC and 71 patients showed less than 50% SRC. Overall cancer-specific 5-year survival was worse for SRC (22.4%, P < 0.0001) and for SRC > 50% (13.6%, P = 0.0001) compared with ADC. Complete resection was achieved in 86.5% of patients (n = 697) in ADC, 69.5% (n = 57) in SRC < 50%, and 78.1% (n = 25) in SRC > 50% (vs ADC, respectively, P < 0.0001 and P = 0.1801). In 379 pN + R0 patients, the median number of positive lymph nodes was comparable between ADC and SRC < 50% (4 vs 5, P = 0.207) or SRC > 50% (4 vs 8, P = 0.077). Compared with ADC, SRC > 50% showed more pN3s (30% vs 61%, P = 0.006), higher recurrence (56% vs 42% for ADC, P = 0.003), and local-regional recurrences (29% vs 16%, P = 0.002). Pretreatment biopsies were unreliable to define the presence of SRC > 50% (sensitivity = 56.3%, positive predictive value = 43.9%). Conclusions:SRCs are aggressive neoplasms associated with poorer prognosis than other ADCs after primary esophagectomy. Because our data suggest that pretreatment biopsies failed to reliably define presence of SRC > 50%, presence of SRCs in pretreatment biopsies seems to be of no use to define treatment strategy or prognosis.

Assessing the relationships between health-related quality of life and postoperative length of hospital stay after oesophagectomy for cancer of the oesophagus and the gastro-oesophageal junction

OBJECTIVES To evaluate baseline health-related quality of life (HRQL) factors that influence short-term outcome after oesophagectomy for cancer of the oesophagus and gastro-oesophageal junction and the effects of postoperative length of hospital stay on postoperative HRQL, as perceived by the patients themselves. METHODS Four hundred and fifty-five patients operated on with curative intent between January 2005 and December 2009 were analysed. HRQL scores were obtained by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30 and oesophageal-specific symptoms (OES-18) questionnaires at baseline (=day before surgery) and 3-monthly post-surgery for the first year. RESULTS There were 372 males and 83 females, with a mean age of 63.1 years. Hospital mortality was 3.7% (17 patients). When analysing postoperative length of stay (LOS), a median of 10 days was found. In a multivariable analysis, using a binary logistic regression model, independent prognosticators for a longer LOS (>10 days) were: medical [hazard ratio, HR, 6.2 (3.62-10.56); P < 0.0001] and surgical [HR 2.79 (1.70-4.59); P < 0.0001] morbidity, readmittance to intensive care unit [HR 33.82 (4.55-251.21); P = 0.001] and poor physical functioning [HR 1.89 (1.14-3.14); P = 0.014]. Postoperatively, patients with early discharge (LOS <10 days) indicated, at 3 and 12 months postoperatively, significant better HRQL scores in the functional scales (physical, emotional, social and role functioning) and in symptoms scales (fatigue, nausea, dyspnoea appetite loss and dry mouth) when compared with LOS >10 days. Return to the level of the reference population scores was achieved at 1 year in the LOS ≤10 days for almost all the scales, but not in the LOS >10 days group. CONCLUSIONS A better perception of preoperative physical functioning might have a beneficial effect on LOS. Our data, furthermore, suggest that early discharge correlates with improved postoperative HRQL outcomes. A clear decrease of the HRQL is seen at 3 months after the surgery, particularly in the LOS >10 days group. Generally, return to the level of the reference population scores is achieved at 1 year in the LOS ≤10 days, but not in the LOS >10 days group.

Central tumour location should be considered when comparing N1 upstaging between thoracoscopic and open surgery for clinical stage I non-small-cell lung cancer

OBJECTIVES Nodal upstaging is a quality indicator for oncological thoracic surgery and is found in up to 25% of patients with clinical stage I (cStage-I) non-small-cell lung cancer (NSCLC). In large retrospective series, lower N1 upstaging was reported after video-assisted thoracic surgery (VATS) resections. We studied the impact of central primary tumour location on nodal upstaging in cStage-I NSCLC. METHODS Consecutive patients operated for cStage-I NSCLC were selected from a prospectively managed surgical database. Tumour location was classified as central if the lesion was visible during standard video bronchoscopy. A nodal station mapping was drawn for each patient based on final pathological examination. Univariable and additive multivariable binary logistic regression analyses were performed. RESULTS Between 2007-2014, 334 patients underwent anatomical resection for cStage-I NSCLC, either by open thoracotomy (n = 158) or by VATS (n = 176; conversion rate 1.7%). All patients underwent imaging with [(18)F]-fluorodeoxyglucose positron emission tomography and computer tomography. Invasive mediastinal staging was performed in 24.6% of patients. There were more central tumours in the open group (24.1%, n = 38) compared with the VATS group (4.5%, n = 8). There was no significant difference between the number (mean ± standard deviation) of nodal stations examined (open 5 ± 1.9 vs VATS 5 ± 1.7, P = 0.99). Pathological nodal upstaging was found in 15.9% (n = 53) of cStage-I patients. Nodal pN1 and pN2 upstaging were 13.3 and 8.2%, respectively, for the open group, and 6.3 and 4.5%, respectively, for the VATS group. In 32.6% (n = 15/46) of patients with a central cStage-I tumour pN1, upstaging was found. A binary logistic regression model (including tumour location, technique, tumour size, gender and histology) showed that only tumour location had a significant impact on pN1 upstaging [peripheral versus central; odds ratio (OR) 5.07 (confidence interval, CI: 1.89-13.60), P = 0.001], while surgical technique had no significant impact [VATS versus open; OR 0.74 (CI: 0.31-1.78), P = 0.50]. CONCLUSIONS The number of lymph node stations examined during VATS resections is similar to open resections for cStage-I NSCLC. Almost one-third of the patients with a central cStage-I NSCLC were upstaged to pN1. Tumour location was the only independent variable for pN1 upstaging in logistic regression analysis. It is a potential bias in retrospective studies and should therefore be accounted for when comparing different surgical resection techniques for cStage-I NSCLC.

Donor–recipient matching in lung transplantation: which variables are important?

OBJECTIVES Donor to recipient (D/R) matching in lung transplantation (LTx) is usually directed by blood group (identity or compatibility) and predicted total lung capacity (pTLC) based on height and age. Other donor (D) and recipient (R) characteristics such as cytomegalovirus (CMV) serology (±), gender [male (M)/ female (F)] and age are often ignored, but the impact of D/R mismatch for these variables and their combinations on outcome is less investigated. METHODS The early and late outcomes in 461 lung recipients (149 single-lung and 312 double-lung) transplanted between July 1991 and December 2009 were explored, comparing different D/R combinations for gender (M/F), age (<20/21 to 45/≥ 45 years), CMV (±), blood group (identical/compatible) and pTLC (-9%Δ, +11%Δ). RESULTS Overall 5-, 10-, 15- and 20-year survival rates were 69, 50, 37 and 37%, respectively, and were significantly better in females {HR [95% confidence interval (CI)]: 0.5 (0.3-0.9); P = 0.023} and worse in older recipients [HR (95% CI): 1.6 (1.2-2.2); P = 0.003]. On univariate analysis, survival was significantly worse in recipients with gender opposite to that of the donor (39% for mismatch vs 51% for match at 10 years; P = 0.04), but not for other D/R matching variables: age (P = 0.89), pTLC (P = 0.14), CMV (P = 0.15), blood group (P = 0.82) and their combinations. The best survival at 5 years was seen in female donor (DF)/female recipient (RF) (80%), the worst in DF/male recipient (RM) (47%), and intermediate in male donor (DM)/RF (72%) and DM/RM (63%); P = 0.0001. On multivariate analysis, D/R gender mismatch was found to be the sole negative predictive factor for survival with an 80% increased risk of mortality [HR (95% CI): 1.8 (1.1-2.8); P = 0.01]. CONCLUSIONS In our patient cohort, survival after LTx was superior in female and younger recipients. D/R gender mismatch may be an important prognostic factor for long-term outcome. A gender combination of DF/RM should be avoided. The exact reasons for these differences remain speculative.

Can extracapsular lymph node involvement be a tool to fine-tune pN1 for adenocarcinoma of the oesophagus and gastro-oesophageal junction in the Union Internationale contre le Cancer (UICC) TNM 7th edition?

OBJECTIVES The current (7th) International Union Against Cancer (UICC) pN staging system is based on the number of positive lymph nodes but does not take into consideration the characteristics of the metastatic lymph nodes itself. In particular, it has been suggested that tumour penetration beyond the lymph node capsule in metastatic lymph nodes, which is also called extracapsular lymph node involvement, has a prognostic impact. The aim of the current study was to assess the prognostic value of extracapsular (EC) and intracapsular (IC) lymph node involvement (LNI) in adenocarcinoma of the oesophagus and gastro-oesophageal junction (GOJ) and to assess its potential impact on the 7th edition of the UICC TNM manual. METHODS From 2000 to 2010, all consecutive adenocarcinoma patients with primary R0-resection (n = 499) were prospectively included for analysis. The number of resected lymph nodes, number of positive lymph nodes and number of EC-LNI/IC-LNI were determined. Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the positive lymph node. RESULTS Two hundred and eighteen (43%) patients had positive lymph nodes. Cancer-specific 5-year survival in lymph node-positive patients was significantly (P < 0.0001) worse compared with lymph node-negative patients, being 88.3 vs 28.7%, respectively. In 128 (58.7%) cases EC-LNI was detected. EC-LNI showed significantly worse cancer-specific 5-year survival compared with IC-LNI, 19.6 vs 44.0% (P < 0.0001). In the pN1 category (1 or 2 positive LNs-UICC stages IIB and IIIA), this was 30.4% vs 58%; (P = 0.029). In higher pN categories, this effect was no longer noticed. Integrating these findings into an adapted TNM classification resulted in improved homogeneity, monotonicity of gradients and discriminatory ability indicating an improved performance of the staging system. CONCLUSIONS EC-LNI is associated with worse survival compared with IC-LNI. EC-LNI patients show survival rates that are more closely associated with the current TNM stage IIIB, while IC-LNI patients have a survival more similar to TNM stage IIB. Incorporating the EC-IC factor in the TNM classification results in an increased performance of the TNM model. Further confirmation from other centres is required within the context of future adaptations of the UICC/AJCC (American Joint Committee on Cancer) staging system for oesophageal cancer.

Primary atrial fibrosarcoma of the heart

The primary fibrosarcoma of the heart is a rare tumor. There are no exact numbers about its incidence, but even among malignant cardiac tumors, only around 3% are fibrosarcomata. Symptoms are nonspecific with signs of right or left heart failure depending on localization. Diagnosis is thereby often delayed. Primary treatment of choice is surgery, followed by several possible postsurgical adjuvant strategies. Survival is poor with a mean of about 11 months.

Validation of a new approach for mortality risk assessment in oesophagectomy for cancer based on age- and gender-corrected body mass index

OBJECTIVES We developed a new algorithm to identify high-risk patients for underweight after oesophagectomy for cancer. Patients were assigned to an age-gender-specific body mass index percentile (AG-BMI) which is then used in a survival analysis. This model was able to identify patients more at risk for being underweight in comparison with the classically used BMI. It shows a worse overall survival (OS) in patients with a preoperative AG-BMI < 10th percentile. The aim of this study is to validate this new model based on a cohort of patients from an external high-volume institution specialized in oesophageal cancer surgery. METHODS The validation cohort consists of 407 patients operated on between 1999 and 2012 with the prerequisite data to calculate AG-BMI and OS. The base cohort consisted of 642 consecutive patients, operated on in our institution between 2005 and 2010. Age, gender, height and weight on the day before surgery were used to calculate the BMI and the AG-BMI. OS was analysed and a multivariate analysis was performed. RESULTS Incidence rates of the AG-BMI < 10th percentile risk-patients in the validation cohort showed similar results to our original results (17.8 vs 17.2% for the base cohort) with a similar significant OS difference between at-risk patients and not-at-risk patients (P < 0.001). Multivariate analysis found the same five independent prognosticators for OS in both datasets: age, early versus advanced disease, resection status, number of positive lymph nodes and the AG-BMI 10th percentile, but not BMI itself. In the validation cohort, gender was identified as an additional independent prognosticator. The worse OS survival in AG-BMI < 10th percentile in both patient populations was related to a significantly higher number of deaths without oesophageal cancer recurrence. CONCLUSIONS This study validates the newly developed AG-BMI model to predict more accurately a subgroup of patients at risk for worse survival after oesophagectomy. Improved perioperative identification of risk factors for poorer OS could help to develop perioperative strategies to reduce these risks.

Options for Esophageal Replacement

Abstract Esophagectomy followed by reconstruction is considered one of the most challenging interventions on the alimentary tract. Today most esophagectomies are performed for cancer of the esophagus and gastroesophageal junction. Other indications are decompensated achalasic megaeesophagus, sequelae of caustic burns, after multiple redo surgeries for reflux. The stomach, shaped into a narrow gastric tube, is the most commonly used conduit for reconstruction due to its favorable length, reliable vascular supply, the need for only one single anastomosis, and, in general, good to excellent sustainable quality of deglutition and life. However, dependent on each individual patients particularities, reconstruction may require to choose another conduit. Colon and jejunum—sometimes to be used as an isolated loop with free vascular anastomosis or as composite grafts—are the available alternatives. Tubular skin flaps in an extremely rare situation may become the last resort option. Combined with a multitude of different access routes, including the recent minimally invasive techniques, as well as different levels of anastomosis, it is clear that there are myriad options available when planning an esophagectomy and reconstruction. A tailored approach for each individual patient guided by an experienced surgical team that is familiar with all conduits available and able to adapt to every situation in order to offer the patient the best possible type of reconstruction is the key to success. This chapter provides an in-depth description of the techniques and results of the whole spectrum of options for esophageal replacement.

The resident’s point of view in the learning curve of thymic MIS: why should I learn it?

Minimally invasive surgery (MIS) in thoracic surgery became quite popular during the last years. The aim of introducing and performing more MIS is to reduce surgical trauma, pain and complications in patients. Training in MIS increases operative time and thus cost in theatre but thus improves with experience. For a resident, the cases should be well selected with experienced supervision in a suitable setting with supporting staff and optimal instruments. Understanding the anatomy of the lung, using simulators, and attending workshops makes the learning curve shorter.