[Metastatic Cardiac Tumor in the Left Atrium from Esophageal Cancer].

Metastatic cardiac lesions are clinically silent and are usually found a necropsy. The most common primary tumor resulting in cardiac metastases is carcinoma of the lung, with there being only a few reports of metastases from esophageal cancer. We report two cases of metastatic cardiac tumors in the left atrium from esophageal cancer and perform a review of the literature. Case 1:A 62-year-old woman underwent esophagectomy and adjuvant chemotherapy. No other metastases were observed. Case 2:A 49-year-old man also underwent esophagectomy and adjuvant chemotherapy for lymph node and liver metastases. In both patients, the left atrial tumors were detected on recent follow-up computed tomography. Left atrial tumors often cause cerebral emboli with neurological sequelae. Therefore, surgical resection and cryo-ablation for the prevention of local recurrence were performed on the metastatic tumors. Local recurrence was not observed after the surgery in both patients. Although chemotherapy is usu-ally the most beneficial treatment for metastatic cardiac lesions, left atrial tumor should be treated with surgical resection because of the high risk of cerebral emboli. We suggest that surgical resection with cryo-ablation may prevent local recurrence.

Comparison of Transcarotid vs. Transfemoral Transcatheter Aortic Valve Implantation.

BACKGROUND: Recently, the carotid artery has been used as an alternative approach for transcatheter aortic valve implantation (TAVI). The aim of this study was to prove the safety and feasibility of transcarotid (TC) vs. transfemoral (TF) TAVI. Methods and Results: This retrospective study enrolled 726 consecutive patients with severe symptomatic aortic stenosis. All patients underwent TC-TAVI or TF-TAVI at Hôpital Haut-Lévèque, Bordeaux Heart University Hospital between September 2012 and October 2017. The TC-TAVI (n=83) and TF-TAVI (n=643) groups were compared statistically. The EuroSCORE II was significantly higher (8.2±6.7 vs. 6.4±5.5; P=0.007) and rates of current smoking, dyslipidemia and peripheral arterial disease were higher in the TC-TAVI than TF-TAVI group. All TC-TAVIs and 9.3% of TF-TAVIs were performed under general anesthesia. Radiation time was significantly shorter in the TC-TAVI than TF-TAVI group (14.5±6.0 vs. 23.0±10.8 min; P<0.001). Postimplant balloon valvuloplasty was performed more frequently in the TF-TAVI than TC-TAVI group (7.2% vs. 19.4%; P=0.006). Postoperative echocardiographic data were similar between the 2 groups, and there were no significant differences in 30-day mortality (8.4% vs. 5.0%; P=0.189) or stroke rate (1.2% vs. 2.6%; P=0.428) between the TF-TAVI and TC-TAVI groups. CONCLUSIONS: The feasibility and 30-day safety of TC-TAVI and TF-TAVI are similar. When TF-TAVI is not suitable anatomically for a particular patient, TC-TAVI is a preferable alternative.

The long-term outcomes of partial arch repair using the frozen elephant trunk technique for distal arch aortic aneurysm.

PURPOSE: The purpose of this study was to evaluate the long-term results of partial arch repair using the frozen elephant trunk (FET) technique for distal arch aortic aneurysm and to examine the late complications. METHODS: Thirty-eight patients with true distal arch aortic aneurysms were repaired with FET introduced through an incision in the proximal arch aorta. Follow-up computed tomography was performed every 6 or 12 months in 36 surviving patients. The maximum dimension of the excluded aneurysmal space was measured to determine whether the aneurysmal space had decreased or disappeared. Late complications were also evaluated during the long-term follow-up. RESULTS: There was 1 hospital death (2.6%) and 1 (2.6%) case of paraplegia. There were 2 late sudden deaths (5.2%) thought to be due to aneurysm rupture and arrhythmia. Postoperative serial-computed tomography showed shrinkage of the excluded aneurysmal space in 33 of 36 patients. Late aneurysmal formation occurred in the anastomotic site in three patients. One patient underwent thoracic endovascular stent grafting 10 years after surgery, 1 patient had total arch replacement 9 years after surgery, and 1 died due to rupture. CONCLUSION: Frozen elephant trunk was found to be a useful alternative for treating true distal arch aortic aneurysm. However, we must be alert for late aneurysmal formation at the incision site.

Abdominal organ protection strategy for aortic arch aneurysm surgery.

INTRODUCTION: Body temperature maintained during open distal anastomosis in patients who undergo aortic surgery has been showing an upward trend; however, a higher temperature may increase visceral organ and spinal cord injury. Distal perfusion may reduce abdominal organ injury, especially acute kidney injury (AKI). METHODS: From 2009 to 2016, 56 patients who underwent ascending aortic and/or aortic arch surgery were enrolled. Open distal anastomosis was performed using one of three protection strategies: 1) systemic temperature of 25°C followed by selective cerebral perfusion (SCP) with lower body circulatory arrest (Group CA25, n=27); 2) systemic temperature of 28°C followed by SCP with lower body circulatory arrest (Group CA28, n=4); and 3) systemic temperature of 28°C followed by SCP with distal aortic perfusion (Group DP, n=25). RESULTS: During the postoperative course, levels of blood urea nitrogen, creatinine, liver enzymes, lactate dehydrogenase and lactate in Groups CA28 and CA25 were significantly higher than those in Group DP. AKI defined by the AKI Network occurred in 28 cases (50%) and 3 cases required permanent hemodialysis. AKI was significantly higher in Groups CA25 and CA28 than in Group DP (p=0.026). Mid-term follow-up showed that patients who developed postoperative AKI were more likely to suffer from cardiovascular events. CONCLUSIONS: Distal perfusion during open distal anastomosis reduced kidney and liver injury after thoracic aortic surgery despite an increased body temperature of up to 28°C. This strategy may be useful to prevent AKI, liver dysfunction, the need for hemodialysis and multiple organ failure and could improve mid-term results.

[Redo Valve Replacement of Wada-Cutter Prosthetic Valve at Tricuspid Valve Position 47 Years After Implantation;Report of a Case].

We experienced an explantation of Wada-Cutter prosthetic tilting disk valve of 47 years after implantation. The patient was 53 years old female who underwent the 1st operation for Ebstein's anomaly, which included tricuspid valve replacement (TVR), closure of atrial septal defect (ASD) and posterior annulorrhaphy when she was 6 years old. She was doing well after the 1st operation without symptom,but dyspnea and systemic edema worsened recently though increased admission of diuretics. Echocardiography revealed severe tricuspid valve stenosis, severe tricuspid valve insufficiency, and increased right atrium volume. The tilting disk of the valve was almost fixed. The patient underwent repeat TVR. The explanted Wada-Cutter valve was covered by pannus the whole casing and disk. The structure of the valve was preserved but the occlusion disk was almost fixed by pannus formation, not distorted or dislodged.

Preoperative Tissue Doppler Imaging-Derived Atrial Conduction Time Predicts Postoperative Atrial Fibrillation in Patients Undergoing Mitral Valve Surgery for Mitral Valve Regurgitation.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery and may result in stroke, heart failure and poor prognosis. This study evaluated a novel index of total atrial conduction time derived from the P-wave onset (lead II) to the peak A' wave on tissue Doppler imaging (PA-TDI duration) in patients undergoing mitral valve surgery (MVS) for mitral valve regurgitation. METHODS AND RESULTS: Seventy-three patients undergoing MVS had transthoracic echocardiography with tissue Doppler imaging preoperatively and were monitored postoperatively with continuous electrocardiographic telemetry for 14 days. Preoperative characteristics, echocardiographic data, operative data and postoperative findings were compared between patients with (n=44) and without (n=29) POAF. Postoperative cardiac events were higher in patients with than without POAF (12/44, 27% vs. 3/29, 10%; P=0.0798) and cerebral events occurred in only 2 POAF patients. On multivariate analysis the independent predictors of POAF were degenerative disease etiology (OR, 4.61; 95% CI: 1.41-15.0; P=0.0112) and PA-TDI duration (OR, 1.04; 95% CI: 1.01-1.07; P=0.0048). On ROC curve analysis a PA-TDI cut-off of 159.4 ms was optimal for predicting POAF. CONCLUSIONS: PA-TDI duration was an independent predictor of POAF after MVS. Patients with PA-TDI duration >159.4 ms should be considered high risk and treated appropriately to improve outcome.

Efficacy of cardiopulmonary rehabilitation with adaptive servo-ventilation in patients undergoing off-pump coronary artery bypass grafting.

BACKGROUND: Postoperative complications after cardiac surgery increase mortality. This study aimed to evaluate the efficacy of cardiopulmonary rehabilitation with adaptive servo-ventilation (ASV) in patients undergoing off-pump coronary artery bypass grafting (OPCAB). METHODS AND RESULTS: A total of 66 patients undergoing OPCAB were enrolled and divided into 2 groups according to the use of ASV (ASV group, 30 patients; non-ASV group, 36 patients). During the perioperative period, all patients undertook cardiopulmonary rehabilitation. ASV was used from postoperative day (POD) 1 to POD5. Hemodynamics showed a different pattern in the 2 groups. Blood pressure (BP) on POD6 in the ASV group was significantly lower than that in the non-ASV group (systolic BP, 112.9±12.6 vs. 126.2±15.8 mmHg, P=0.0006; diastolic BP, 62.3±9.1 vs. 67.6±9.3 mmHg, P=0.0277). The incidence of postoperative atrial fibrillation (POAF) was lower in the ASV group than in the non-ASV group (10% vs. 33%, P=0.0377). The duration of oxygen inhalation in the ASV group was significantly shorter than that in the non-ASV group (5.1±2.2 vs. 7.6±6.0 days, P=0.0238). The duration of postoperative hospitalization was significantly shorter in the ASV group than in the non-ASV group (23.5±6.6 vs. 29.0±13.1 days, P=0.0392). CONCLUSIONS: Cardiopulmonary rehabilitation with ASV after OPCAB reduces both POAF occurrence and the duration of hospitalization.

A case of Heyde syndrome: resolution following aortic valve replacement.

Heyde syndrome is a triad of aortic stenosis, acquired coagulopathy, and anemia due to bleeding from intestinal angiodysplasia. Here we describe a case of this syndrome. An 80-year-old woman with severe aortic stenosis was referred to our department for an aortic valve replacement. She suffered from recurrent iron-deficiency anemia and required transfusions every 2 weeks. Gastroscopy and colonoscopy were normal with the exception of angiodysplasia without bleeding in the cecum. After aortic valve replacement her anemia was resolved. She was discharged on postoperative day 22. No transfusions were needed after the procedure. To date, her hemoglobin has remained stable at >10 mg/dL.

Using hemoglobin vesicles to treat operative hemorrhagic shock after pneu- monectomy in dog models: an experimental study.

Hemoglobin vesicles (HbVs), considered as red blood cell substitutes, are liposomes encapsulating purified hemoglobin, with a phospholipid bilayer membrane (diameter: 250 nm; P50, 28 Torr). In this study, we aimed to investigate HbV function during hemorrhagic shock in lung resection and analyze the details of oxygen delivery. Left pneumonectomy was performed in dogs under mechanical ventilation, followed by rapid exsanguination of approximately 30% of the total circulating blood volume, which led to shock, reducing the mean arterial pressure (MAP) by approximately 60% of baseline. Subsequently, either 5% human serum albumin (HSA) or HbVs suspended in 5% HSA were infused for resuscitation. The MAP only recovered to 75% of baseline after HSA administration, but fully recovered (100%) after HbV administration, with significant differences between the groups (P < 0.005). Oxygen delivery was restored in the HbV group and was significantly higher than that in the HSA group (P < 0.0001). The infusion of HbVs dispersed in a 5% HSA solution compensated for the rapid loss of approximately 30% of the total circulating blood volume in a dog pneumonectomy model, even with impaired lung function. Thus, HbVs can be used for resuscitation from hemorrhagic shock during thoracic surgery.

ECMO Alone Versus ECPELLA in Patients Affected by Cardiogenic Shock: The Multicenter EVACS Study.

The objective was to investigate the outcomes of concomitant venoarterial extracorporeal membrane oxygenation (ECMO) and left ventricular unloading with Impella (ECPELLA) compared with ECMO alone to treat patients affected by cardiogenic shock. Data from patients needing mechanical circulatory support from 4 international centers were analyzed. Of 438 patients included, ECMO alone and ECPELLA were adopted in 319 (72.8%) and 119 (27.2%) patients, respectively. Propensity score matching analysis identified 95 pairs. In the matched cohort, 30-day mortality rates in the ECMO and ECPELLA were 49.5% and 43.2% ( P = 0.467). The incidences of complications did not differ significantly between groups ( P = 0.877, P = 0.629, P = 1.000, respectively). After a median follow-up of 0.18 years (interquartile range 0.02-2.55), the use of ECPELLA was associated with similar mortality compared with ECMO alone (hazard ratio 0.81, 95% confidence interval 0.54-1.20, P = 0.285), with 1-year overall survival rates of 51.3% and 46.6%, for ECPELLA and ECMO alone, respectively. ECMO alone and ECPELLA are both effective strategies in patients needing mechanical circulatory support for cardiogenic shock, showing similar rates of early and mid-term survival.

Pulmonary pleomorphic carcinoma producing granulocyte-macrophage colony-stimulating factor: report of a case.

We report a case of lung cancer producing granulocyte-macrophage colony-stimulating factor (GM-CSF). The patient, a 55-year-old woman, was found to have leukocytosis (leukocytes 28.8 × 10(3)/mm3) with eosinophilia (eosinophils 24.5%) without any evidence of infection or allergy. The serum concentration of GM-CSF was elevated to 44 pg/ml (normal range <2.0 pg/ml), which might have induced the leukocytosis and eosinophilia. We performed left pneumonectomy and diagnosed a pleomorphic carcinoma with p-T2bN0M0, based on histological examination of the resected tumor. Immunohistochemical examination revealed GM-CSF. The serum level of GM-CSF decreased to within the normal range 8 days after surgery. At the time of writing, 16 months after the surgery, she was alive without disease. To our knowledge, this represents the first case report of a GM-CSF-producing tumor effectively treated by surgical resection.

Early reperfusion with hemoglobin vesicles into tracheal subepithelial capillaries in a mouse tracheal transplant model.

Hemoglobin vesicles (HbVs), liposomes containing concentrated hemoglobin extracted from outdated human red blood cells (RBC), are artificial oxygen carriers with a small particle size. To evaluate the reperfusion of capillaries with HbVs in a tracheal transplant model and compare it with that of RBC. Isogenic mice were used as donors and recipients in a parallel trachea transplant model. Both ends of the donor trachea were anastomosed end-laterally to the recipient trachea to form in parallel. After transplantation, 0.3 mL of HbV solution (Hb concentration, 10 g/dL) was administered via the tail vein. The recipients were euthanized 1, 4, 6, and 8 h after surgery (n = 5 in each group). The tracheas were harvested, and tracheal subepithelial capillaries (SEC) reperfusion was histologically evaluated. A significant number of particles defined as HbV by electron microscopy were observed in the SEC of the grafted tracheas 4 h after the transplant surgery and HbV administration when no RBC were found in the SECs. The number increased 6 and 8 h later. Our findings suggest that HbVs, which are smaller than RBC, can reperfuse the capillaries of grafts earlier than RBCs after transplantation and contribute to the oxygenation of transplanted tissues.

Unilateral versus bilateral cerebral perfusion during aortic surgery for acute type A aortic dissection: a multicentre study.

OBJECTIVES: The aim of this retrospective multicentre study was to investigate and compare clinical outcomes of unilateral and bilateral antegrade cerebral perfusion (ACP) strategies on cerebral protection during surgery for type A aortic dissection. METHODS: Data from 646 patients who underwent surgical repair of thoracic type A aortic dissection using unilateral and bilateral ACP with moderate hypothermic circulatory arrest in 3 cardiac surgical institutions between 2008 and 2018 were analysed. Propensity matching was performed to assess which technique ensured better outcomes. RESULTS: Unilateral and bilateral ACP techniques were performed in 250 (39%) and in 396 (61%) patients, respectively. Propensity score analysis identified 189 matched pairs. In the matched cohort, the lowest core temperature was 27.5°C and 28°C in the bilateral and unilateral groups, respectively (P < 0.001). The unilateral technique required significantly shorter aortic cross-clamp and cardiopulmonary bypass times than bilateral technique [82 min vs 100 min (P < 0.001); 170 min vs 195 min (P < 0.001)]. The 30-day mortality was comparable (P = 0.325). The bilateral group reported a significantly higher incidence of permanent neurologic deficits (P < 0.001), left brain hemisphere stroke (P = 0.007) and all-combined complications (P < 0.001). Ten-year survival was comparable (P = 0.45). CONCLUSIONS: Unilateral and bilateral ACP are both valid brain protection strategies in the landscape of aortic arch surgery. While admitting all the study limitations, unilateral technique could offer some clinical advantages. CLINICAL REGISTRATION NUMBER: 76049.

KL-6 and CEA levels in epithelial lining fluid microsamples predict response to gefitinib in patients with advanced non-small cell lung cancer.

BACKGROUND AND OBJECTIVE: Both Krebs von den Lungen-6 (KL-6) and carcinoembryonic antigen (CEA) are known to be tumour markers in non-small cell lung cancer (NSCLC). The aim of the present study was to assess whether or not intrabronchial epithelial lining fluid (ELF) levels of these markers predicted tumour response better than serum levels in patients with advanced NSCLC treated with gefitinib. METHODS: ELF samples were obtained both from near the tumour and from the contralateral lung using a bronchoscopic microsampling technique, before and 2 weeks after the start of gefitinib treatment. Serum samples were taken concurrently. Among the 22 patients enrolled in the study, 14 (64%) showed partial responses or stabilization of disease with gefitinib treatment (treatment responders), while 8 (36%) showed progression of disease (treatment non-responders), 4 weeks after the start of treatment. RESULTS: ELF KL-6 levels near the tumour decreased significantly after 2 weeks in the treatment responders group (P = 0.011), whereas there was a marginal increase in the treatment non-responders group (P = 0.049). ELF CEA levels near the tumour decreased significantly after 2 weeks in the treatment responders group (P = 0.004), whereas there was no significant change in the treatment non-responders group. For both markers, neither the serum levels nor the levels in contralateral ELF showed any significant changes in either group of patients. CONCLUSIONS: Both KL-6 and CEA levels in ELF near the tumour predicted tumour response in NSCLC patients treated with gefitinib, whereas serum levels did not.

How many pathological T1N0M0 non-small cell lung cancers can be completely resected in one segment? Special reference to high-resolution computed tomography findings.

PURPOSE: Although segmentectomy is attempted for small non-small cell lung cancer (NSCLC) tumors, no reports have so far described how many of these tumors can be candidates for a successful resection by single segmentectomy. METHODS: In all, 135 patients with peripheral p-T1N0M0 NSCLC were examined. The tumors were classified into five groups divided by every 0.5-cm increase in size. Tumor locations were classified into two groups - limited to within one segment and extended beyond one segment - based on the identification of whether pulmonary vessels and the bronchi were involved in the tumors on high-resolution computed tomography. Differences in the proportion of tumors limited within one segment between tumors smaller and larger than each class of tumor size were assessed. RESULTS: The tumor sizes were 0-1.0 cm in 8 tumors, 1.1-1.5 cm in 27, 1.6-2.0 cm in 35, 2.1-2.5 cm in 34, and 2.6-3.0 cm in 31 tumors. Of these 135 tumors, 92 (65%) were limited to one segment, whereas 48 (35%) had extended beyond one segment. When the tumor size was less than 30 mm, the proportion of tumor limited within one segment did not show any significant difference depending on the size of the tumor. CONCLUSIONS: More than one-third of p-T1N0M0 NSCLC tumors extended beyond one segment, irrespective of size. It is therefore noteworthy that resection of up to two segments or lobectomy should be undertaken for prevention of local recurrence in patients with p-T1N0M0 peripheral NSCLC.

ADAM28 is a serological and histochemical marker for non-small-cell lung cancers.

ADAM28 (a disintegrin and metalloproteinase 28) is over-expressed in non-small-cell lung cancer (NSCLC) with correlation to cancer cell proliferation, tumor size and lymph node metastasis. The present study was aimed to develop an enzyme-linked immunosorbent assay (ELISA) system for diagnosis and monitoring of NSCLC. Our ELISA specifically measured ADAM28, showing negligible cross-reactivity with other metalloproteinases. The ADAM28 level in the NSCLC tissue was remarkably 36.9-fold higher than that in the non-neoplastic lung tissue (p < 0.001). The serum level was significantly 4.6-fold higher in the NSCLC patients (5.41 +/- 8.62 ng/ml; n = 102) than in the control subjects (1.17 +/- 0.93 ng/ml; n = 20) (p < 0.001), and increased with progress of tumor stage (p < 0.001). The level was also significantly higher in the patients with recurrent carcinoma than the control (p < 0.001) and in the patients with lymph node metastasis than those without metastasis (p < 0.001). The sensitivity, false-negative rate and AUC for ADAM28 were better than those for carcinoembryonic antigen. The combination of both assays improved the sensitivity, specificity, false-positive and false-negative rates for NSCLC. There was a positive correlation between the ADAM28 level measured by ELISA system and the degree of immunostaining in the lung adenocarcinomas with a size of

Association between false lumen segmental arteries and spinal cord ischemia in type A acute aortic dissection.

BACKGROUND: Spinal cord ischemia (SCI) and paraplegia are complications of surgery for type A acute aortic dissection (TAAAD). Since the segmental arteries play a key role in SCI, this study evaluated the association between SCI and false lumen segmental arteries (FLSAs: segmental arteries originating from the false lumen). METHODS: The study included 101 consecutive TAAAD patients (mean age, 66±13; range, 34-89 years) who underwent surgery from January 2011 to April 2017. The diagnosis of TAAAD and the number of FSLAs were determined by preoperative computed tomography (CT). Patients were divided into two groups according to the number of FLSAs at the Th9-L2 level: Group A (N.=13), ≥8 FLSAs; and group B (N.=88), ≤7 FLSAs. Preoperative, perioperative, and postoperative findings were compared between the groups, and risk factors for SCI were evaluated. RESULTS: The frequency of preoperative paralysis was significantly higher in Group A than Group B (P=.0070). The overall incidence of postoperative SCI was 8% (8/101) and significantly higher in Group A than Group B (5/13 [45%] vs. 3/88 (4%), P<0.0001). Hospital mortality was 8% (8/101) and significantly higher in Group A than Group B (3/13 [23%] vs. 5/88 [6%], P=.0302). Multivariate analysis showed that the independent risk factors for SCI were ≥8 FLSAs at Th9-L2 (odds ratio [OR], 20.4; 95% confidence interval [95% CI], 3.34-124.9, P=0.0011) and diabetes mellitus (OR, 22.3; 95% CI, 1.69-294.5; P=0.0184). CONCLUSIONS: In patients who underwent surgery for TAAAD, ≥8 FLSAs at the Th9-L2 levels on preoperative CT was a risk factor for SCI.

Immediate effects of systemic administration of normal and high O2-affinity haemoglobin vesicles as a transfusion alternative in a rat pneumonectomy model.

BACKGROUND: Haemoglobin vesicles (HbVs) are red blood cell (RBC) substitutes with a phospholipid bilayer membrane and a polyethylene modified surface (diameter=250 nm; P50=28 Torr). They can be preserved for years and can be used in patients of all blood types without the risk of infection. Their oxygen affinity can be modified by changing the allosteric effectors. METHODS: Left pneumonectomy was performed under mechanical ventilation on rats, followed by rapid exsanguination of ~30% of the total circulating blood volume. Rat RBCs shed in 5% human serum albumin (HSA) solution (rat RBC), HbV with high oxygen affinity in 5% albumin solution (low-P50 HbV, P50=9 Torr), normal HbV suspended in 5% albumin (HbV, P50=28 Torr) or 5% HSA was infused for resuscitation. Haemodynamics and oxygenation were evaluated. RESULTS: Systemic arterial blood pressure significantly decreased after exsanguination and increased after each infusion. In the HbV, low-P50 HbV and rat RBC groups, all rats were liberated from mechanical ventilation and blood pressure was stabilised, whereas 50% of the rats in the HSA group died within 1 hour after weaning from mechanical ventilation. The PaO2 in arterial blood for 1 hour after liberation from mechanical ventilation in the rat RBC, HbV and low-P50 HbV groups was 59.4±12.5, 58.3±10.1 and 70.5±14.5 mm Hg, respectively. The PaO2 in the low-P50 HbV group was significantly higher than those in the rat RBC and HbV groups (p=0.05 for both). Serum lactate elevations due to hypoxic damage were minimised by HbV, low-P50 HbV as well as rat RBCs. CONCLUSIONS: The oxygen-carrying ability of HbV was comparable to that of rat RBCs, even under impaired lung function after pneumonectomy. HbVs with high oxygen affinity may have more beneficial effects on oxygenation in pulmonary resection.

Exacerbation of bleomycin-induced injury and fibrosis by pneumonectomy in the residual lung of mice.

BACKGROUND: Lung resection after induction chemotherapy and/or radiotherapy for down-staging of locally advanced lung cancer can be complicated with lethal interstitial pneumonia. We studied the effects of pneumonectomy on bleomycin-induced lung injury and fibrosis in mice. METHODS: The mice underwent left pneumonectomy or a sham thoracotomy after intratracheal administration of saline or bleomycin. Lung permeability index, wet-to-dry weight ratio, histological changes, collagen contents, and concentrations of inflammatory mediators and cell counts in broncho-alveolar lavage (BAL) fluid were assessed in the residual right lung 7 d after surgery. RESULTS: The index of capillary permeability, lung water content, and inflammatory cell counts in BAL fluid were significantly increased by pneumonectomy. These measurements were highest in the mice with both pneumonectomy and intratracheal administration of bleomycin. Similarly, fibrotic change in lung pathology, as well as an increase in lung collagen content, was most prominent in the mice exposed to both interventions. The BAL fluid concentrations of interleukin-1beta, interleukin-6, RANTES, and high mobility group box 1 were significantly increased by pneumonectomy and enhanced by the additional administration of bleomycin. CONCLUSIONS: The results of this study indicate that pneumonectomy alone causes noncritical lung injury, which amplifies the inflammatory response to bleomycin and promotes lung fibrosis. Several inflammatory mediators appear to be involved in the exacerbation of bleomycin-induced lung injury and fibrosis.

Systemic administration of hemoglobin vesicle elevates tumor tissue oxygen tension and modifies tumor response to irradiation.

BACKGROUND: We have developed a phospholipid liposome vesicle encapsulating concentrated human hemoglobin (hemoglobin vesicle, HbV) as an artificial oxygen carrier, as an alternative to red cell transfusion. We have verified its oxygen transporting capability in a variety of preclinical models. Recent evidence suggests that artificial oxygen carriers may also be applicable for better oxygenation of ischemic or hypoxic tissues including tumors. To our knowledge, tumor oxygenation using a liposome-type artificial oxygen carrier has not been closely tested. In the present study, we tested whether systemic HbV administration changes tumor tissue oxygen tension, and if it modifies tumor response to irradiation. MATERIALS AND METHODS: Lewis lung carcinoma was grown subcutaneously in the left hindleg of C57BL/6 mice. Experiments were initiated when the tumors reached approximately 8 mm. All experiments were done under room air. Tumor tissue oxygen tension was measured by phosphorescence quenching up to 45 min after systemic sample administration (saline: n = 5; HbV: n = 5; HbV containing methemoglobin (metHbV): n = 4; HbV with high oxygen affinity (lowP50HbV): n = 8) and compared between samples. To test the effects on irradiation response, samples (saline: n = 7; HbV: n = 7; metHbV: n = 7; lowP50HbV: n = 7) were administered prior to single 20-Gy irradiation, and tumor growth was compared. RESULTS: Tumor tissue oxygen tension transiently increased approximately 2-fold after HbV administration in comparison to other samples. Tumor growth was marginally delayed after irradiation by prior administration of HbV in comparison to other samples. HbV administration without irradiation did not affect significant tumor growth delay. CONCLUSIONS: These results correlatively suggest that HbV augmented tumor growth delay following irradiation, at least in part, by affecting tumor tissue oxygen tension.