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.

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.

Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients.

PURPOSE: To compare the accuracy of computed tomography-(CT) scan and the radiolabeled glucose analog 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) visually correlated with CT (PET + CT) in the locoregional lymph node (LN) staging of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Sixty-eight patients with potentially operable NSCLC underwent thoracic CT, PET, and invasive surgical staging (ISS). Imaging studies were read prospectively and blinded to the surgical and pathologic data. A five-point visual scale was used for the interpretation of LNs on PET. Afterwards, with knowledge of the pathology, the relationship between standardized uptake values (SUVs) and the presence of metastasis in LNs was explored in a receiver operating characteristic (ROC) analysis, and the likelihood ratios (LRs) for SUVs of LNs were determined. RESULTS: ISS was available for 690 LN stations. CT correctly identified the nodal stage in 40 of 68 patients (59%), with understaging in 12 patients and overstaging in 16 patients. PET + CT was accurate in 59 patients (87%), with understaging in five patients and overstaging in four patients. In the detection of locally advanced disease (N2/N3), the sensitivity, specificity, and accuracy of CT were 75%, 63%, and 68%, respectively. For PET + CT, this was 93%, 95%, and 94% (P = .0004). In the ROC curve, the best SUV threshold to distinguish benign from malignant LNs was 4.40. The analysis with this SUV threshold was not superior to the use of a five-point visual scale. The LR of a SUV less than 3.5 in an LN was 0.152; for a SUV between 3.5 and 4.5, it was 3.157; and for a SUV greater than 4.5, it was 253.096. CONCLUSION: PET + CT is significantly more accurate than CT alone in LN staging of NSCLC. A five-point visual scale is as accurate as the use of an SUV threshold for LNs in the distinction between benign and malignant nodes. The very high negative predictive value of mediastinal PET could reduce the need for mediastinal ISS in NSCLC substantially.

Clinical prognostic factors in surgically treated stage IIIA-N2 non-small cell lung cancer: analysis of the literature.

There remains controversy on the prognostic value of several common clinical factors in NSCLC patients with resected N2-disease. The aim of this paper is to give a comprehensive overview of the available data on this issue. Literature data on surgically treated N2-NSCLC-patients from 1980-1995, peer reviewed and listed in Index Medicus, were analysed. Reported and calculated or estimated survival data were indexed. Eighteen series were selected: in 12 of them, direct comparisons between survival curves of subgroups are reported; six contained sufficient data to make comparisons of survivors at 5 years; three of them also made a multivariate Cox model. The analysis of prognostic factors in a single study was often hampered by the limited number of patients. Nonetheless, it could be concluded that patients with a clinical N0- or N1-status (so-called unforeseen N2) do better. There was no clear difference between patients undergoing lobectomy or pneumonectomy. There was strong evidence that N2-patients with a less advanced primary tumour (T-stage) have a better prognosis, and this is the case for all operable T-stages (T1 versus T2, T1 versus T3, T2 versus T3). Squamous cell type was a favourable prognostic factor, as was the presence of only one metastatic mediastinal lymph node station or absence of metastases to the subcarinal nodes. There was some evidence that the presence of extracapsular spread in metastatic MLN is an unfavourable finding. Stratification for these prognostic factors could help in the planning of future trials on combined modality treatment in N2-NSCLC.

Practical approach to patients presenting with multiple synchronous suspect lung lesions: a reflection on the current TNM classification based on 54 cases with complete follow-up.

OBJECTIVES: To examine the survival after surgical treatment of patients presenting with two synchronous suspect lung lesions, and to reflect on the recent TNM classification, which has upgraded patients with two malignant lung lesions of the same histology into the T4 (both lesions in the same ipsilateral lobe) or M1 (different lobes or lungs) category. METHODS: Retrieval of all consecutive patients with a diagnosis of two synchronous suspect lung lesions in the prospective database of the Leuven Lung Cancer Group in the interval between 1990 and 1994. Analysis of characteristics and survival of all patients, who underwent surgical resection with intention to cure for both lesions. RESULTS: Forty-eight of 54 patients had surgical resection with curative intent. Thirty-five of these proved to have two malignant lesions, in 13 the second lesion was benign. The 5-year survival rate in the patients with two malignant lesions was 33% (95% CI: 17-49). The median survival time was 28 months. Although the number of patients in the subgroups was small, there were no obvious differences between patients with two lesions in the same or in different lobes, if a complete resection could be achieved. CONCLUSIONS: An aggressive surgical approach in carefully selected patients presenting with two suspect pulmonary lesions can be rewarding. Although some degree of upstaging is appropriate in patients with two malignant lung tumours of the same histology, their current stage IIIB or IV classification probably underestimates their prospects for long-term survival after radical resection.

Pulmonary cell death in warm ischemic rabbit lung is related to the alveolar oxygen reserve.

BACKGROUND: If lungs could be retrieved for transplantation from non-heart-beating cadavers, the shortage of donors might be significantly alleviated. METHODS: We studied the effect of different postmortem lung conditions on pulmonary cell death. Lungs from 208 New Zealand white rabbits were flushed with trypan blue vital dye solution at intervals after circulatory arrest, fixed, and mounted for histologic examination. Pulmonary cells were judged to be viable on the basis of their ability to exclude trypan blue dye. In the control group, lungs were excised immediately after death and immersed in cold (4 degrees C) saline solution. In the other groups, cadavers were left at room temperature with lungs deflated, ventilated with room air or 100% oxygen or 100% nitrogen, or inflated with room air or 100% oxygen. RESULTS: There was a gradual increase in percentage (mean +/- SEM) of nonviable cells in the control group from 2.5%+/-0.9% (preischemic value) to 18.1%+/-2.8% at 24 hours after death (p < 0.001). In cadavers with lungs deflated, 79.7%+/-2.1% of cells were nonviable at 24 hours after circulatory arrest (p < 0.001 versus control group). In contrast, room air-ventilated cadavers showed only 21.4%+/-2.7% nonviable cells at this interval (p < 0.001 versus deflated group; not significant versus control group). Values in oxygen-ventilated animals were similar. Nitrogen-ventilated cadavers, however, had significantly more nonviable lung cells (73.8%+/-3.2%; p < 0.001 vs room air and oxygen-ventilated group, not significant vs deflated group). Oxygen-inflated lungs showed a parallel decrease in cell viability up to 4 hours after death when compared with room air-inflated cadaveric lungs, but thereafter more cells became nonviable in the latter group (11.1%+/-0.7% vs 19.6%+/-3.2% at 6 hours and 48.7%+/-7.2% vs 75.5%+/-4.6% at 24 hours, respectively; p < 0.01). CONCLUSIONS: Postmortem room air ventilation is as good as oxygen ventilation in delaying pulmonary cell death, and its effect is comparable to cold storage; nitrogen ventilation, however, is ineffective and not different from deflation; oxygen inflation will preserve ischemic cells for longer intervals as opposed to room air inflation. Therefore the alveolar oxygen reserve seems to be the critical factor to protect-the lung parenchyma from warm ischemic damage.

Chronic symptoms after subtotal or partial oesophagectomy: diagnosis and treatment.

In the great majority of patients, subtotal or partial oesophagectomy is performed because of malignancy, for which wide local excision and additional lymphadenectomy are indicated. Except in patients with early lesions, the vagal nerves have to be sacrificed bilaterally, which can induce a great variety of functional abnormalities. The continuity of the gastrointestinal tract is preferably restored by using a whole-stomach interposition or gastric tube. The oesophago-gastric anastomosis is critically vascularized and carries a significant risk of benign fibrotic stricturing, especially when it is located in the neck. Acid or biliary reflux may result in persistent oesophagitis and the development of Barrett's metaplasia in the remnant oesophagus. The reservoir capacity of the gastric tube is limited, whereas the emptying rate can vary considerably, leading to complaints of either gastric retention or intestinal dumping. It is not clear whether or not gastric drainage procedures are beneficial. Recurrent nerve damage with vocal cord paralysis may result in aspiration and recurrent pulmonary infection. The permanent threat of recurrent disease combined with the substantial physical impact of an extensive surgical procedure inducing a wide range of functional disturbances of the gastrointestinal tract has a great influence on quality of life, at least temporarily. The late complications of anastomotic stricturing and the functional consequences of bilateral vagotomy, gastric tubulization and gastric pull-up will be reviewed. Moreover, the general and specific changes in quality of life will be addressed.

Thoracoscopic surgery: the Belgian experience.

Despite the already wide experience with video-assisted techniques in laparoscopic surgery, video-assisted thoracic surgery only recently came to be developed. This is clearly seen in a survey reflecting the experience among Belgian surgeons. A majority of the surgeons (63%) had limited experience (1 to 5 interventions), and only 28.5% had fairly considerable (between 11 and 20 interventions) or considerable (more than 20 interventions) experience. The majority of interventions performed were the treatment of pneumothorax, lung biopsies, wedge resections, and intrathoracic staging procedures, accounting for 209 (70%) of the 296 interventions collected in this survey. The remaining interventions display a wide variety of different thoracic procedures including lobectomy (4) and esophagectomy (20) for carcinoma. The overall technical success rate was 91% in this survey. Our own experience with 71 interventions or attempts reflects the same evolution with an overall technical success rate in 85% (60 patients). Pneumothorax was the most frequently performed intervention (35 patients), with a technical success rate of 94.5% (32 patients). Recurrences requiring further treatment occurred in 5 of the 32 patients (14.3%). All recurrences occurred before endostaplers were available, after which there were no failures in 12 consecutive cases. Other procedures successfully performed were lung biopsy/wedge resection (6), lung cancer staging procedures (3), lobectomy (1), hemothorax (3), chest wall neurinoma (2), sympathectomy (5), dorsal mediastinal neurinoma (1), thymectomy (1), esophagectomy (3), benign esophageal tumor enucleation (2), and Belsey Mark IV antireflux procedure (1). Furthermore, special emphasis was given to the development of video-assisted mediastinoscopy, which greatly facilitates teaching and interpreting this operation. Endoscopic myotomy using endostaplers was performed in 2 patients with Zenker's diverticulum. From our experience, however, it becomes clear that thoracoscopic approaches do not always result in a distinct benefit for the patient, as these procedures are more time consuming and usually require one-lung ventilation (probably the cause of the only fatal outcome in this series: a lung biopsy in an 85-year-old patient). In conclusion, video-assisted thoracic and thoracoscopic surgery is a new surgical modality offering new perspectives. However, careful patient selection and the same expertise as in open procedures are essential in determining the final outcome of each procedure.

Thoracoscopic thymectomy in autoimmune myasthesia: results of left-sided approach.

BACKGROUND: We undertook to analyze the results of video-assisted thoracoscopic thymectomy through a left-sided approach in patients with autoimmune myasthenia. METHODS: Between 1993 and 1997, 31 patients underwent thoracoscopic thymectomy by a uniform left-sided approach. There were 8 men and 23 women with a mean age of 34 +/- 12 years. RESULTS: Preoperative duration of disease was 14.8 +/- 11 months. There were no operative deaths or major complications. The mean hospital stay was 5.2 +/- 2.8 days. Mean follow-up was 39.6 +/- 15 months and was 100% complete. At 48 months, remission and improvement rates were 36% and 96%, respectively. Shorter duration of symptoms (< 12 months) correlated with improved outcome (13 of 13 patients versus 10 of 14 patients; p = 0.036). Age, sex, Osserman class, corticosteroid therapy, presence of ectopic thymic tissue, and temporary postoperative symptom increase (deterioration) did not affect outcome. CONCLUSIONS: Thoracoscopic thymectomy facilitated the goal of early thymectomy. Through a left-sided approach, improvement or remission was achieved in more than 95% of the patients. Thoracoscopic thymectomy should be considered a valid less invasive alternative to the most radical open approaches.

Delay of adenosine triphosphate depletion and hypoxanthine formation in rabbit lung after death.

BACKGROUND: If lungs could be retrieved for transplantation from non-heart-beating cadavers, the shortage of donors might be significantly alleviated. METHODS: Adenosine triphosphate (ATP) and hypoxanthine levels were measured postmortem in rabbit lungs comparing deflation (group 1), ventilation with room air (group 2), inflation with room air (group 3), ventilation with oxygen (group 4), ventilation with cooled air (group 5), deflation plus cadaver cooling (group 6), and cooling by pulmonary arterial flush (group 7). RESULTS: The level of ATP dropped to 25.9% and HYP increased elevenfold at 30 minutes in group 1 but remained constant during 24 hours in group 7. The ATP catabolism beyond 2 hours postmortem appeared less in group 2 compared with group 3 (3.58 +/- 1.24 versus 0.39 +/- 0.08 mumol/g dry weight for ATP and 3.03 +/- 0.49 versus 7.64 +/- 0.94 mumol/g dry weight for hypoxanthine at 24 hours, respectively; p < 0.05). Cadaver cooling significantly slowed ATP catabolism. Changes in ATP level were similar in groups 2, 4, and 5. CONCLUSIONS: These data suggest that in the non-heart-beating cadaver (1) cooling, ventilation, and inflation can delay ATP catabolism; (2) postmortem ventilation but not inflation for more than 2 hours will inhibit further ATP breakdown; (3) ventilation with either oxygen or cooled air is not more beneficial than room air ventilation; and (4) cold flush more than cadaver cooling will prevent ATP depletion.

Effect of inflation on adenosine triphosphate catabolism and lactate production during normothermic lung ischemia.

Although few biochemical data comparing adenosine triphosphate (ATP) catabolism or lactate production in isolated deflated versus inflated lung tissue are available, most transplant centers preserve their donor lungs inflated. We measured ATP level (using high-performance liquid chromatography), energy charge, and lactate level during 2 hours of normothermic ischemia in deflated lung tissue (n = 6), in lung tissue inflated with room air (n = 6), and in lung tissue inflated with 100% oxygen (n = 6). To determine the onset of anaerobic metabolism in lung tissue inflated with 100% O2, ATP and lactate levels were measured in another group (n = 6) during 8 hours of normothermic ischemia. Rabbit lungs were flushed in situ with a modified Krebs-Henseleit solution (60 mL/kg). They were isolated and immersed in 0.9% NaCl at 37 degrees C. In deflated lung tissue, ATP level (control value, 9.4 +/- 0.58 mumol/g dry wt) decreased and lactate level (control value, 5.6 +/- 1.16 mumol/g dry wt) increased after 15 minutes of ischemia (ATP, 5.2 +/- 0.86 mumol/g dry wt; lactate, 13.3 +/- 1.58 mumol/g dry wt). When the lung was stored inflated with room air, ATP breakdown and increase of lactate concentration only occurred after 90 minutes of normothermic ischemia (at 60 minutes: ATP, 8.0 +/- 0.58 mumol/g dry wt; lactate, 6.3 +/- 1.1 mumol/g dry wt). In lungs stored inflated with 100% O2, ATP breakdown and lactate accumulation only occurred after 5 hours of normothermic ischemia (at 4 hours: ATP, 8.1 +/- 0.74 mumol/g dry wt; lactate, 5.9 +/- 1.28 mumol/g dry wt).(ABSTRACT TRUNCATED AT 250 WORDS)

Survival and prognostic factors in resected N2 non-small cell lung cancer: a study of 140 cases. Leuven Lung Cancer Group.

BACKGROUND: The selection of stage IIIA N2 non-small cell lung cancer patients for primary surgical treatment remains controversial. METHODS: One hundred forty patients with resected non-small cell lung cancer who eventually proved to have pathologic N2 disease were studied with a univariate and multivariate analysis of prognostic factors. RESULTS: Nineteen patients had a positive mediastinoscopy; the others had a preoperative N0 or N1 stage. Complete resection rate was 80.7%. Five-year survival was 20.8% (95% confidence interval, 17.2% to 24.4%), 32.2% in mediastinoscopy-negative patients. In the univariate analysis, clinical N stage at mediastinoscopy, complete resection, performance status, T stage, number of metastatic levels in adenocarcinoma, and nodal capsule rupture were important factors. In a multivariate model, survival was worse in case of higher T stage (relative risk = 1.43), lower performance status (relative risk = 1.37), involvement of more than one node level (relative risk = 1.68), nonsquamous histology (relative risk = 1.29) and clinical N2 stage (relative risk = 1.43). Long-term survival was unlikely when lactic dehydrogenase or carcinoembryonic antigen levels were elevated. CONCLUSIONS: In clinical N0 or N1 cancer, complete resection resulted in reasonable survival prospects. In patients with N2 disease discovered at mediastinoscopy, surgical treatment was only worthwhile in case of minimal N2. Several unfavorable prognostic factors could be identified in the univariate analysis and confirmed in a multivariate Cox model.

External cooling of warm ischemic rabbit lungs after death.

BACKGROUND: If lungs could be retrieved for transplantation after circulatory arrest, the shortage of donors might be significantly alleviated. However, in such non-heart-beating donors, there is great concern that even a short period of warm ischemia will be deleterious for lung tissue, jeopardizing the transplant recipient. It was the purpose of this study to look for the efficacy of different methods of lung cooling inside a cadaver after circulatory arrest. METHODS: New Zealand white rabbits were sacrificed with an intravenous overdose of pentobarbital and left at room temperature. Subcutaneous, rectal, lung core, lung surface, and endobronchial temperatures were measured at intervals after death. Cooling of the lung during ischemia differed between groups (n = 6 in each group): lungs left deflated at room temperature (24 degrees C) (group 1 = control non-heart-beating donors), lungs ventilated with cooled (4 degrees C) room air (group 2), lungs left deflated plus topical cooling (1 degree C) of both the cadaver and its lungs (group 3), and lungs flushed in situ immediately after circulatory arrest with a cold (4 degrees C) crystalloid solution followed by ex vivo deflated storage in cold (1 degree C) saline solution (group 4 = control heart-beating donors). RESULTS: There was a slow decline in lung core, lung surface, and endobronchial temperatures toward room temperature in group 1 (1.5 degrees +/- 0.0 degree C/h, 1.8 degrees +/- 0.2 degree C/h, and 1.9 degrees +/- 0.1 degree C/h, respectively). In contrast, all three lung temperatures immediately ( < 5 minutes) dropped to less than 10 degrees C in group 4. Hypothermic ventilation (group 2) decreased endobronchial temperature (p < 0.05 at 30 minutes) but not lung surface, rectal, or subcutaneous temperature when compared with group 1. Cooling rate for lung surface and endobronchial temperatures during the first 4 hours after death was faster (p < 0.01) in group 3 (6.6 degrees +/- 0.3 degree C/h and 6.1 degrees +/- 0.2 degree C/h, respectively) when compared with group 2 (2.5 degrees +/- 0.3 degree C/h and 3.9 degrees +/- 0.1 degree C/h, respectively), but slower (p < 0.001) when compared with group 4 (9.2 degrees +/- 0.1 degree C/h and 8.7 degrees +/- 0.1 degree C/h, respectively). CONCLUSIONS: These data demonstrate that in the non-heart-beating donor, (1) in situ cold flush will result in immediate cooling of the lung, (2) ventilation with cooled air will only accelerate the decline in endobronchial temperature but has no effect on lung surface temperature, and (3) topical cooling of the cadaver is more efficacious in decreasing lung temperature than hypothermic ventilation.

Extended preservation of ischemic pulmonary graft by postmortem alveolar expansion.

BACKGROUND: If lungs could be retrieved for transplantation from non-heart-beating cadavers, the shortage of donors might be significantly alleviated. METHODS: Peak airway pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and wet to dry weight ratio were measured during delayed hypothermic crystalloid flush in rabbit lungs (n = 6) at successive intervals after death comparing cadavers with lungs left deflated (group 1), inflated with room air (group 2) or 100% oxygen (group 4), or ventilated with room air (group 3), or 100% nitrogen (group 5), or 100% oxygen (group 6). RESULTS: There was a gradual increase in mean pulmonary artery pressure and pulmonary vascular resistance with longer postmortem intervals in all study groups (p = not significant, group 1 versus group 2 versus group 3). There was also a gradual increase in peak airway pressure and wet-to-dry weight ratio over time in all groups, which reflected edema formation during flush (airway pressure, from 14.5 +/- 1.0 cm H2O to 53.7 +/- 12.2 cm H2O, and wet-to-dry weight ratio, from 3.6 +/- 0.1 to 11.5 +/- 1.2, in group 1 at 0 and 6 hours postmortem, respectively; p < 0.05). Compared with group 1, however, the increase in groups 2 and 3 was much slower (airway pressure, 20.9 +/- 0.5 cm H2O and 18.8 +/- 1.2 cm H2O, and wet-to-dry weight ratio, 5.2 +/- 0.3 and 4.6 +/- 0.4 at 6 hours postmortem, respectively; p < 0.05 versus group 1 and p = not significant, group 2 versus group 3). Airway pressure and wet-to-dry weight ratio did not differ between groups 2 and 4 or between groups 3, 5, and 6. CONCLUSIONS: These data suggest that (1) pulmonary edema will develop in atelectatic lungs if hypothermic flush is delayed for 2 hours after death, (2) postmortem inflation is as good as ventilation in prolonging warm ischemic tolerance, (3) inflation with oxygen or ventilation with nitrogen or oxygen is no different from that with room air, and (4) therefore, prevention of alveolar collapse appears to be the critical factor in protecting the lung from warm ischemic damage independent of continued oxygen delivery.

Fetal cardiac tamponade due to an intrapericardial teratoma.

A case of an intrapericardial tumor diagnosed in utero at 26 weeks of gestation is presented. The prenatal echocardiographic follow-up of an incipient hydrops fetalis determined the management and the emergency surgical treatment. Histologically, the tumor appeared to be a benign teratoma, grade I. In the postoperative period an unexpected mediastinal tumor was found and removed later. This tumor also appeared to be a benign teratoma, grade 0. Both teratomas were independent and therefore primary.

Ischemic preconditioning enhances donor lung preservation in the rabbit.

OBJECTIVE: Ischemic preconditioning achieved by brief periods of ischemia followed by reperfusion before a prolonged period of ischemia, is well known to reduce myocardial damage. We investigated whether ischemic preconditioning of the lung could also attenuate ischemia-reperfusion injury following pulmonary preservation. METHODS: Transient ischemia of the right lung was achieved in rabbits (n = 4 in each group) by occluding the main bronchus and pulmonary artery, followed by reperfusion according to a protocol that differed between study groups: group 1 (control), 45 min ventilation; group 2, 30 min ventilation, 5 min ischemia and 10 min reperfusion; group 3, three periods of 5 min ischemia and 10 min reperfusion; group 4, five periods of 3 min ischemia and 6 min reperfusion. Donor lungs were then flushed with a crystalloid solution followed by inflated storage at 37 degrees C for 2 h. The function of the right lung was assessed during reperfusion for 2 h with homologous, diluted and deoxygenated blood in an isolated, pressure-limited, and room-air ventilated model. RESULTS: Significant differences (P < 0.0001) were observed between groups 1 and 2 vs. groups 3 and 4 in veno-arterial oxygen pressure gradient (29 +/- 6 and 24 +/- 6 mmHg vs. 124 +/- 24 and 132 +/- 14 mmHg, respectively), and in weight gain (88 +/- 13 and 98 +/- 13% vs. 44 +/- 9 and 29 +/- 3%, respectively) after 1 h of reperfusion, and in wet-to-dry weight ratio (15.5 +/- 1.5 and 14.3 +/- 0.4 vs. 10.1 +/- 1.6 and 9.0 +/- 0.8, respectively) at the end of reperfusion. No significant differences in any of these parameters were observed between group 1 vs. group 2 neither between group 3 vs. group 4. CONCLUSIONS: These data suggest: (1) That 15 min, but not 5 min of transient ischemia prior to pulmonary preservation can significantly reduce edema in the lung graft upon reperfusion, thus improving oxygenation capacity and (2) although not significant, this beneficial effect seems to be slightly better with more repetitive periods of transient ischemia. Further research is warranted to investigate whether ischemic preconditioning in the human organ donor may become a new strategy to protect lung tissue during a planned ischemic event as in pulmonary transplantation.

Alveolar expansion itself but not continuous oxygen supply enhances postmortem preservation of pulmonary grafts.

OBJECTIVE: If lungs could be retrieved for transplant after circulatory arrest, the shortage of donors might be significantly alleviated. Great controversy still exists concerning the optimal mode of preservation of pulmonary grafts in these non-heart-beating donors. METHODS: Graft function was measured in an isolated room air-ventilated rabbit lung model during reperfusion with homologous, diluted (Hb +/- 8.0 g/dl) and deoxygenated (PaO2 +/- 40 mmHg) blood up to 4 h. Five groups of cadavers (n = 4 in each group) were studied: In the control group, lungs were immediately reperfused. In the other groups, cadavers were left at room temperature for 4 h after death with lungs either deflated (group 1), inflated with room air (group 2), or ventilated with room air (group 3) or 100% nitrogen (group 4). RESULTS: After 1 h of reperfusion, significant differences were noted between group 1 and groups 2, 3, and 4 in peak airway pressure (27 +/- 5 cm H2O vs. 15 +/- 1 cm H2O, 17 +/- 2 cm H2O, and 16 +/- 1 cm H2O, respectively; P < 0.05), in weight gain (137 +/- 24 vs. 31 +/- 7, 30 +/- 3, and 30 +/- 2%, respectively; P < 0.05), and in veno-arterial oxygen pressure gradient (9 +/- 5 vs. 95 +/- 13, 96 +/- 7 and 96 +/- 4 mmHg, respectively; P < 0.05). Also, wet-to-dry weight ratio at end of reperfusion was significantly different (10.2 +/- 1.0 vs. 6.0 +/- 0.3. 5.2 +/- 0.3 and 5.4 +/- 0.5, respectively; P < 0.05). No significant differences in any of these parameters were observed between groups 2, 3, and 4. CONCLUSIONS: These data suggest that: (1) pulmonary edema will develop in atelectatic lungs if reperfusion is delayed for 4 h after death; (2) postmortem room air-inflation is as good as ventilation in prolonging warm ischemic tolerance; (3) ventilation with room air is no different from that with nitrogen; (4) therefore, prevention of alveolar collapse appears to be the critical factor in protecting the warm ischemic lung from reperfusion injury independent of continuous oxygen supply.

Tracheal side effects of endoscopic balloon tracheal occlusion in the fetal lamb model.

OBJECTIVE: To evaluate effects of in-utero endoluminal balloon tracheal occlusion (TO) as suggested for the treatment of Congenital Diaphragmatic Hernia (CDH) on the higher airways of a fetal lamb model. STUDY DESIGN: Fetuses from time-dated pregnant ewes underwent at 94 days (term=145 days) in-utero tracheal occlusion. In study animals an endoluminal, detachable balloon was placed by tracheoscopy. For that purpose a 1.2mm fibre-optic, semi-rigid endoscope and a medically graded latex balloon were used. In group I (n=9) lambs were delivered after 2 weeks. In group II (n=8) the tracheal occlusion was released after 2 weeks, to allow in-utero recovery until term. In positive control animals (group III; n=5) the trachea was clipped at 98 days and fetuses were harvested near term by cesarean section. A total of 17 contralateral littermates in multiple pregnancies served as negative controls. After macroscopic inspection of the trachea, sections were evaluated by light microscopy. Alterations were scored with an empirical interval score for each of the different anatomical elements in the fetal trachea (epithelium, submucosa, cartilage, pars membranacea). RESULTS: For the animal experiments in group I, all balloons were found in place and according to the pulmonary response they were obstructive. Tracheas were macroscopically dilated by the plug mainly due to elongation of the pars membranacea. The total histologic score was correlated to the increase in circumference (mean increase: 3.0mm). In nearly all cases, the tracheal epithelium at the level of the plug had lost its typical folding pattern. In 44% of cases, local epithelial defects were observed and in 33% of cases there was squamous metaplasia. A chronic inflammatory response was present in over half of the cases, sometimes with giant cell reaction. In group II (the in-utero recovery group) the total score was significantly lower than in group I, with much less prominent unfolding and absence of epithelial defects. Squamous metaplastia was still present in half of the cases; whereas inflammatory responses were less frequent. In group III the trachea expanded normally after removal of the clip. The epithelium had compacted folds, and cilia were well preserved. In two animals however, intraluminal synechia were observed. Below the level of occlusion animals of groups I and II all showed areas of unfolding, but without metaplasia or epithelial defects. CONCLUSION: Tracheal obstruction by means of endoluminal plugging has been suggested as an alternative in-utero treatment for congenital diagphragmatic hernia. The balloon causes mild epithelial changes, such as unfolding, limited epithelial defects (<25% of the exposure surface) and local inflammatory changes. These changes disappear nearly completely following in-utero unplugging during the rest of gestation. Unfolding of the epithelium is also seen in the trachea under the plug.