Increased urinary albumin indicating urothelial leakage following intravesical bacillus Calmette-Guérin therapy for superficial bladder cancer

Summary This study on the increase in albumin in the urine of patients with superficial bladder cancer after intravesical bacillus Calmette-Guérin (BCG) treatment was initiated on the basis of two facts. First, extravasation of serum albumin could be expected as a result of the BCG-induced delayed-type hypersensitivity reaction in the bladder wall. Second, appearance of albumin in the urine was a possibility as cytokines also appear in the urine, although probably after being produced suburothelially by infiltrating leukocytes. Albumin and the cytokines interleukin (IL) 1, IL2, IL6, and tumor necrosis factor alpha (TNF) were determined in urine from 20 patients treated with 6 weekly intravesical BCG instillations, collected prior to each instillation and 2, 4, 6, 8, 12, and 24h thereafter. The mean concentration of albumin in pre-therapy specimens was 112±118 (range 2–432) g albumin/ml urine, approximating 14±14 g/ mol creatinine (creat) (n=15), which was comparable to the mean pre-instillation value of 16±32 g/mol creat (n=96). A significant increase in urinary albumin during the 6 weeks of BCG treatment was observed (P<0.001). However, a large variation existed between individual patients and in some patients no reaction was seen. Maximum albumin concentrations were observed after instillations 3–6. A significant correlation between albumin and concentration of the cytokines IL1, IL2, IL6, and TNF was found (P<0.01), correlation coefficients (r) being 0.56, 0.56, 0.67, and 0.71 (n=418), respectively. During the first 24h after instillation cytokines and albumin peaked in the following order: TNFIL2albuminIL6IL1. TNF peaked most frequently after 2–4h and IL1 after 6h, while IL2, albumin, and IL6 peaked between these time points. In conclusion, the presence of albumin in urine indicates a leakiness of the bladder wall after repeated BCG instillations. Since albumin was shown to be stable in urine and the assay is relatively simple and cheap, it may be performed in most hospitals. This will allow largescale investigations of the correlation between elevation of urinary albumin and (tumor) response on BCG therapy.     

Antibodies directed at mouse IL-2-R α and β chains act in synergy to abolish T-cell proliferation in vitro and delayed type hypersensitivity reaction in vivo

The anti-mouse IL-2-R chain mAb TM-1 which, by itself, does not affect IL-2-dependent proliferation throught the high affinity mouse IL-2 receptor, was shown to cooperate in a synergistic way with a set of anti-IL-2-R chain mAbs both in vitro and in vivo. In vitro, when associated at equimolar concentrations, the TM-1/anti- mAb association was four to ten times more efficient at inhibiting the proliferation of the CTL-L2 cell line than was a similar concentration of anti- mAb alone. In addition, a bispecific antibody in which a Fab' fragment of TM-1 was covalently linked to a Fab' fragment of one of the anti- mAb (5A2) was shown to be as efficient as the TM-1/5A2 association. The association of TM-1 with 5A2 was also tested in vivo in a sheep red blood cell-induced delayed type hypersensitivity (DTH) model. TM-1 which, by itself, had no effect on DTH, induced a two- to threefold decrease in the doses of 5A2 required to suppress this cell-mediated immune reaction.     

Dexamethasone regulates IL-1β and TNF-α-induced interleukin-8 production in human bone marrow stromal and osteoblast-like cells

We have investigated both constitutive- and cytokine-induced secretion of interleukin-8 (IL-8) and its regulation by dexamethasone and 17-estradiol in normal human bone marrow stromal (HBMS), osteoblast-like cells (hOB), and osteosarcoma MG-63 cells. Although HBMS cells secrete low levels of IL-8 constitutively, treatment with IL-1 and tumor necrosis factor- (TNF-) induced IL-8 secretion. Their effects were synergistic but IL-8 production was not affected by 17-estradiol. Human osteosarcoma MG-63 cells also secreted low levels of IL-8 constitutively; the production was induced by IL-1 and TNF- and was also not affected by 17-estradiol. The magnitude of the response to cytokine stimulation of IL-8 in MG-63 cells was much lower than that of HBMS and hOB cells, indicating differences in response in normal and osteoblastic osteosarcoma cells. Dexamethasone (10^-7 M) significantly inhibited IL-1 plus TNF- stimulated IL-8 production in HBMS, MG-63, and hOB cells. The accumulated results demonstrate that IL-8 is secreted by HBMS, MG-63, and hOB cells, suggesting that IL-8 may play a role in the regulation of bone cell function. These data also emphasize the importance of glucocorticoids in controlling cytokine secretion in HBMS, hOB, and MG-63 cells.     

Cytokine production by the human bladder carcinoma cell line T24 in the presence of bacillus Calmette-Guerin (BCG)

Summary The study was initiated as an in vitro approach to the situation existing during intravesical bacillus Calmette-Guerin (BCG) instillation in patients with superficial bladder cancer. Cytokine secretion of a human bladder carcinoma cell line T24 treated with BCG was investigated. A 24-h treatment of T24 cells with BCG resulted in a tenfold higher secretion of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) when compared with T24 cells treated with Escherichia coli, Streptococcus faecalis or a cell wall preparation of Nocardia rubra (N-CWS). No secretion of IL-1 and IL-2 was detected. Pre-exposing T24 cells to BCG for various periods of time indicated that a minimum exposure time of 0.5–1 h was required to upregulate IL-6 and TNF production. Extending the BCG pre-exposure time to 2 and 3 h further increased the rate of cytokine production. No significant difference was found, however, between the rate of secretion initiated after a 2-h or 3-h pre-exposure period. The amounts of these cytokines secreted in the presence of BCG-conditioned medium did not differ significantly from the constitutively secreted amounts, excluding an effect of products possibly secreted by BCG on the upregulation of IL-6 and TNF. In addition, upregulation of cytokine production appeared to be dependent on the concentration of BCG. The results suggest that cytokines may be produced by urothelial tumor cells after intravesical instillation in patients with superficial bladder cancer, which may play a role in the mode of action of BCG.     

The ultrastructure of the epiphyseal plate

A method of fixation has been developed for the cartilage cells of the epiphyseal plate. Improved preservation of the flattened chondrocytes reveals small vesicles that seem to originate in the rough endoplasmic reticulum and are found in large amounts in the Golgi area. Different types of vacuoles can be distinguished in the Golgi complex, e.g. intermediate vacuoles and large vacuoles, the latter usually containing inclusions. It seems likely that the vesicles and vacuoles each play a specific role in the transport and production of sulfated protein polysaccharides.

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Zusammenfassung Es wurde eine Methode zur Fixation der Knorpelzellen aus der Epiphysenplatte entwickelt. die besser erhaltenen abgeflachten Chondrocyten zeigen kleine Bläschen, welche aus dem groben endoplasmatischen Reticulum zu stammen scheinen und in großen Mengen im Golgi-Bereich vorliegen. Verschiedene Arten von Vacuolen können im Golgi-Apparat unterschieden werden, z.B. intermediate vacuoles und large vacuoles, wobei die letztgenannten gewöhnlich Einschlüsse enthalten. Es ist wahrscheinlich, daß die Bläschen sowie die Vacuolen eine spezifische Rolle beim Transport und der Bildung von sulfatierten Proteinpolysacchariden spielen.

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Résumé Une méthode de fixation des cellules cartilagineuses de la métaphyse est mise au point. Une meilleure préservation des chondrocytes applatis montre de petites vésicules qui semblent naître dans l'ergastoplasme et se trouvent en grande quantité au niveau de l'appareil de Golgi. Différents types de vacuoles sont visibles dans cet appareil, à savoir des vacuoles intermédiaires et de larges vacuoles contenant des inclusions. Il parait probable que les vésicules et vacuoles jouent un rôle spécifique dans le transport et la production de polysaccharides de protéines sulfatées.

     

AneuRx Device Migration: Incidence, Risk Factors, and Consequences

Success after endovascular abdominal aortic aneurysm repair (EVAR) is dependent on device positional stability. The quest for such stability has motivated different endograft designs, and the risk factors entailed remain the subject of debate. This study aims at defining the incidence, risk factors, and clinical implications of device migration after EVAR with the AneuRx® endograft. In this study we included all consecutive 109 patients submitted to primary AneuRx placement for infrarenal aortic or aortoiliac aneurysms. Preoperative computed tomography (CT) scans were reviewed for the following anatomic characteristics: neck length, diameter, angulation, calcification, and thrombus load; and sac diameter and thrombus load. Percentage of device oversizing relative to the proximal neck diameter was determined. All postoperative CT scans were reviewed, and the distance between the lowest renal artery and the craniad end of the device was measured. A 5-mm increase in such distance was considered indicative of device migration. Migration cumulative incidence was estimated by the Kaplan-Meier method, and its association with any of the preoperative anatomical characteristics was tested using Cox proportional hazards models. Median follow-up time was 9 (range, 1-31) months. Migration occurred in nine patients, corresponding to a 15.6% estimated probability of migration at 30 months (SE=5.1%). Migration was associated with the risk of proximal type I endoleak (hazard ratio=3.39, 95% confidence interval=1.46-7.87; p=0.007). This type of endoleak occurred in three of the migration-affected patients (33.3%); all of them were resolved by additional cuff placement at the proximal landing zone. No other migration-related reinterventions were performed. The only significant associations between anatomic factors and device migration probability were the protective effects of longer necks (odds ratio [OR]=0.71 for each additional 5 mm, p=0.045) and longer overlapped portions of neck and device (OR=0.56 for each additional 5 mm, p=0.003). There was a trend toward higher probability of migration among reverse-tapered necks (OR=1.75, p=0.109). Percentage of device oversizing correlated with early neck dilation (between preoperative and first postoperative diameters, correlation coefficient=0.4, p < 0.0001), but not with late neck dilatation (between first postoperative and 1.5-year scan diameters, correlation coefficient=0.29, p=0.112). There was a trend toward higher mean percentage of late dilation among migrators (11.4%, standard error of the mean [SEM] 2.6) than nonmigrators (5.7%, SEM=1) (p=0.08), but both groups had similar mean percentages of early dilation (3%, SEM=1.6%, vs. 5.5%, SEM=0.6%; p=0.365). This result indicates that device migration is not a rare event after AneuRx implantation. This phenomenon is associated with proximal type I endoleaks. Deployment of the endograft immediately below the renal arteries might help to prevent migration, since use of greater lengths of overlapped device relative to the proximal neck has a protective effect. Migration seems to be independent of the degree of device oversizing.Presented at the 29th Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, Sergio M. Sampaio is a recipient of the Edward S. Rogers Clinical Research Fellowship in Vascular Surgery.     

Demonstration of the 5-flap technique

Summary Demonstration of the 5-flap technique which is double opposed Z-plasty and Y – V advancement is presented. A 4×4 gauze serves to demonstrate this technique.The authors dedicate this paper to the dear memory of their teacher, the late Prof. Zvi Neuman, who passed away untimely on March 22, 1977     

PTSD among vietnam veterans: An early look at treatment outcome using direct therapeutic exposure

Vietnam combat veteran inpatients were evaluated after being treated in a PTSD special treatment unit. Selected pretreatment measures that included mental and physical problems, combat variables, PTSD symptoms, and the standard MMPI scales found no clinically meaningful differences between a group that was found to be successes and another group found to be failures, based on predetermined cutoff scores on the VETS scale, a reliable outcome measure for veteran patients. At 3 months post-therapy, a significantly greater number of subjects treated with Direct Therapeutic Exposure (DTE) (flooding therapy) as compared to another group treated with a more conventional individual therapy, were identified as successes as opposed to failures, based on the VETs scale. Also, the number of failures was greater for those treated with the more conventional therapy and the number of successess was greater for those treated with DTE, when compared to all other subjects in the sample. These preliminary results were interpreted as indicating that DTE, when offered as part of an inpatient milieu, shows promise as an effective treatment for chronic/severe combat veteran PTSD sufferers.     

Differentiation of pancreatic ductal carcinoma cells associated with selective expression of protein kinase C isoforms

Background: The signal transduction pathways important in regulating the growth and differentiation of malignant cells are poorly understood. Recent evidence has implicated activation of the protein kinase C (PKC) family of signaling proteins in pancreatic carcinoma during cytokine-induced cytostasis and differentiation. Methods: A human pancreatic adenocarcinoma (HPAC) cell line was exposed to tumor necrosis factor- (TNF-; 40 ng/ml) for 6 days. Cytostasis and viability were confirmed by daily MTT [(3(4,5)-dimethyl-thiazol-2-yl) 2,5-diphenyl-tetrazolium bromide] and trypan exclusion assay. Protein fractions were isolated daily and subjected to immunoblot analysis for the normal (terminally differentiated) pancreatic ductal cell marker carbonic anhydrase II (CA II) as well as specific PKC isoforms (, , , , and). Results: Growth arrest occurred in HPAC cells after exposure to TNF- for 48 h, with viability maintained above 90% throughout the 6-day time course. CA II immunoreactivity was not detected in untreated controls but appeared after 2 days of TNF- exposure, peaking on day 6. Concurrently, TNF- induced the selective downregulation of PKC-, whereas PKC- levels increased. PKC- and PKC- immunoreactivity did not change. The atypical PKC- isoform developed a doublet banding pattern in response to TNF-, although overall PKC- levels did not change. Conclusions: TNF--induced growth arrest and differentiation in HPAC cells is associated with the selective downregulation of PKC- and upregulation of PKC-.Presented at the 48th Annual Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Vertical lengthening of the unilateral cleft lip after a triangular flap repair

Summary A triangular flap repair for unilateral cleft lip is stated to have the potential problem of creating a lip that is too long. Although preoperative measurements were performed with calipers, the gap created in the medial segment was directly measured during the procedure, in order to determine the size of the flap more precisely. Ninety patients with complete unilateral cleft lips underwent a triangular flap repair using this method. The symmetry of the Cupid's bow was evaluated at a follow-up period averaging between six years and three months. Sixty-two lips obtained symmetry and the remaining 28 cases showed a lip which was too long; none of the lips were too short. The comparison between 27 primary palate clefts (UCLA) and 63 primary and secondary palate clefts (UCLP) showed no significant difference in the surgical result. The preoperative shortness of the lip on the cleft side was significantly greater in the too long group (5.01 ± 0.95 mm) than in the symmetry group (4.40 ± 0.87 mm). The width of the flap used was significantly larger in the too long group (3.76 ± 0.79 mm) than in the symmetry group (3.42 ± 0.69 mm). The triangular flap repair with intraoperative measurements is considered to be beneficial, although preoperative measurements provide an optimal design in most cases. It is suggested that the use of a wider triangular flap results in a lip which tends to be too long in spite of the preoperative shortness on the cleft side.     

Cytokines in human milk: Properties and potential effects upon the mammary gland and the neonate

Epidemiologic and immunologic studies of breastfed and nonbreastfed infants and investigations of certain biologic activities in human milk led to the identification of immunomodulating agents in human milk. Among them were the cytokines interleukin-1 (IL-1); IL-6, IL-8, IL-10, granulocyte-colony stimulating factor, macrophage-colony stimulating factor (M-CSF), tumor necrosis factor-, interferon-, epithelial growth factor (EGF), transforming growth factor- (TGF-), and TGF-2. Inteferon- may originate from T cells in milk; EGF, TGF-, TGF-, M-CSF, IL-6, and IL-8 may be produced by mammary gland epithelium. Based upon their known functions, we hypothesize that cytokines influence the development and immunologic function of the mammary gland and the neonate. Thosein vivo functions remain to be defined by future investigations.     

242. Korrelation klinischer und biochemischer Befunde mit dem Schweregrad einer bakteriellen Peritonitis

Zusammenfassung Anhand von Verlaufsdaten 66 chirurgischer Patienten mit einer bakteriologisch gesicherten Peritonitis sollten harte und weiche Kriterien zur Beurteilung des Schweregrades differenziert werden. Untersuchungskriterien: 1) regionale Ausbreitung, 2) Entwicklung eines Organod. Systemversagens, 3) Leukocytose/Thrombopenie, Körpertemperatur, 4) die Plasmamediatoren Endotoxin/Prostaglandin F₂ (PGF₂), 5) Anamnesedauer (Erstsymptom bis OP), 6) Anzahl erforderlicher Reoperationen und 7) Lebensalter. Zuzuordnende Schweregrade: Grad 1: überlebt, Grad 2: mit Komplikationen überlebt, Grad 3: nicht überlebt. Danach erweisen sich als harte Kriterien: 1) Lokalisation, 2) Anamnesedauer, 3) Leukocytose, 4) Endotoxin > 100 Eu/ml, PGF₂ > 500 pg/ml, 5) Körpertemperatur 38,5°C.     

Effect of Intraperitoneal Neutrophils Induced by OK432 on Malignant Ascites

Purpose To evaluate the efficacy of a streptococcal preparation, OK432, on malignant ascites in mice.Methods PC-C203U (PC203) is a preparation of another strain of the streptococcal family, with the lowest antineoplastic action. To examine the survival curves of mice after the inoculation of BAMC-1 tumor cells, we gave intraperitoneal OK432, PC203, or saline as a control. Intraperitonal neutrophils were counted by cytospin, and interleukin-1 (IL-1), interleukin-6 (IL-6), and macrophage inflammatory protein (MIP)-1 were measured by enzyme-linked immunosorbent assay, and 8h after the administration of OK432, PC203, and saline. Using electron microscopy, we examined the greater omental milky spots, where the in situ proliferation of neutrophils or macrophages takes place.Results The OK432 group had the best survival and the control group the worst. The ratio of intraperitoneal neutrophils to BAMC-1 was highest in the OK432 group and lowest in the control group. Quantitative IL-1, IL-6 and MIP-1 levels were correlated closely with survival. Electron microscopic examination of the milky spots revealed massive proliferation of neutrophils in the OK432 group, but not in the PC203 or control groups.Conclusion OK432 effectively activated intraperitoneal neutrophils and a series of immunological chain reactions through an increase in IL-1, IL-6, and MIP-1 levels. Milky spots could have important antitumor effects in terms of the spread of neutrophils.     

Oesophagusvaricenblutungen im Kindes- und Kleinkindalter

Ohne ZusammenfassungOriginalarbeit erscheint im Zentralblatt für Chirurgie.     

Systemic liberation of interleukin-1β and interleukin-1 receptor antagonist in the perioperative phase of liver transplantation

We measured systemic serum levels of interleukin-1 receptor antagonist (IL-1ra), interleukin-1 (IL-1), tumor necrosis factor (TNF-), and interleukin-6 (IL-6) during the preoperative, anhepatic, and postreperfusional phases up to the 7th postoperative day in 60 patients undergoing orthotopic liver transplantation (LTx). In contrast to IL-1, IL-1ra, TNF-, and IL-6 showed a significant elevation in relation to the early phase after reperfusion, while TNF- displayed a high grade of scatter. In addition, IL-1ra levels were significantly elevated during the anhepatic phase. Maximum serum levels were found at 15 min after reperfusion, 120 min after reperfusion, and on the 1st postoperative day, respectively. Serum levels decreased considerably at 24 h and 7 days after reperfusion. The comparative monitoring of systemic cytokine and cytokine antagonist levels, in particular the liberation of IL-1ra and IL-6 may provide useful parameters for the development of new liver preservation theories for LTx.     

Chronic intramedullary infusion of interleukin-1α increases bone mineral content in rats

Interleukin-1 (IL-1) is known to have a potent bone-resorbing activity in vitro, however, results from in vivo studies are conflicting. We performed experiments with the continuous infusion of recombinant IL-1 directly into the femoral bone marrow of rats for 2 weeks and examined its effects on bone by soft X-ray photographs, bone mineral assessment, and histological examination. Infusion of IL-1 at doses greater than 1 g/ml (0.6 ng/hour) caused sclerosis around the infusion site on soft X-ray photographs, and the bone mineral content of IL-1 infused femora was increased significantly. Histologically, extensive periosteal bone formation was observed around the infusion site and small mononuclear cells replaced the normal fat tissue. Infusion of prostaglandin E₂ alone produced intramedullary bone formation more extensively. Simultaneous infusion of IL-1 and indomethacin (10^-3 M; 179 ng/hour) inhibited the increase of bone mineral content (BMC) induced by IL-1. Thus, the chronic intramedullary administration of IL-1 stimulates bone formation, especially in the periosteum, and increases BMC in intact rats.     

37. Kalter Strumaknoten — eine absolute Operationsindikation?

Zusammenfassung Von 1969 bis 1984 haben wir 3972 Schilddrüsenoperationen durchgeführt. 3540 Szintigraphiebefunde konnten retrospektiv ausgewertet werden. In 2013 (57 %) der Fälle lagen ein oder mehrere kalte Knoten vor. Die Malignomincidenz der kalten Knoten lag bei 5,6 %. Bei der Feinnadelpunktion wurde in 17,9 % ein falsch negativer Befund erhoben. Aufgrund der Malignitätsrate der kalten Knoten in unserem Krankengut von 5,6 %, hoher falsch negativen Rate der Feinnadelpunktion und bei vertretbarer postoperativer Komplikationsrate, halten wir eine grundsätzliche Operationsindikation für berechtigt.     

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Background. Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. Methods. We examined the effect of the angiotensin (AT)₁ receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] 140mmHg or diastolic blood pressure [DBP] 90mmHg) and CKD (male, body weight [BW] 60kg: 1.5 SCr < 3.0mg/dl; female or male BW < 60kg: 1.3 SCr < 3.0mg/dl), manifesting proteinuria of 0.5g or more/day. Losartan was administered once daily at doses of 25 to 100mg/day, and amlodipine was given once daily at 2.5 to 5mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. Results. A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group (n = 43), but there was no change in the amlodipine group (n = 43). Analysis of stratified subgroups with proteinuria of 2g or more/day and less than 2g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. Conclusions. Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.     

Use of a pericardial fat pad flap for preventing bronchopleural fistula: An experimental study focusing on the angiogenesis and cytokine production of the fat pad

An experimental study was conducted to determine whether pericardial fat tissue could induce neovascularization and produce cytokines related to tissue repair. Neovascularization was examined using chick chorioallantoic membranes. Pieces of pericardial fat tissue, omentum, and intercostal muscle were individually placed on a number of chorioallantoic membranes and neovascularization induced by each material was assayed 6 days after the implantation. The intensity of neovascularization was in the order of pericardial fat omentum > muscle. Cytokines, such as interleukin 1 (IL-1) and , tumor necrosis factor- (TNF), interferon- (IFN-), and interleukin 6 (IL-6) were assayed in a culture supernatant of pericardial fat tissue. The latter was obtained 24h after the addition of lipopolysaccharide (LPS) following various incubation times. All cytokines other than IFN are known to play a part in tissue repair, whereas IFN is negatively related to tissue repair because it inhibits fibroblast growth. The pericardial fat tissue incubated with LPS produced a certain amount of IL-1 on day 1, and TNF on days 1 and 8, whereafter these values decreased to an undetectable level. Irrespective of the addition of LPS, a large amount of IL-6 was observed in the supernatant of pericardial fat tissue and it was detectable until day 29. On the contrary, INF was not detected at any assay time. These observations suggest that a pericardial fat pad flap could possibly be beneficial in the prevention of bronchopleural fistula after pulmonary resection.