What factors determine the survival of patients with an acute exacerbation of interstitial lung disease after lung cancer resection?

PURPOSES: Acute exacerbation of interstitial pneumonia (AEIP) is a leading cause of death after lung cancer resection in patients with interstitial lung disease. METHODS: We retrospectively analyzed 1763 patients with non-small cell lung cancer with a clinical diagnosis of interstitial lung disease (ILD) who underwent lung cancer resection between 2000 and 2009 at 61 hospitals in Japan. AEIP occurred in 164 of 1763 (9.3%) patients with a mortality rate of 43.9% (72/164). Univariate and multivariate analyses were carried out to identify possible risk factors of fatal AEIP. We then analyzed the 164 patients who developed postoperative AEIP and identified the preoperative and postoperative risk factors. RESULTS: A multivariate regression analysis identified that the sex, percent vital capacity, neoadjuvant radiation, preoperative history of AEIP, preoperative use of steroids, usual interstitial pneumonia pattern on CT, and surgical procedures were independent preoperative risk factors for death due to AEIP. ILD patients with emphysema somehow showed a lower risk of fatal AEIP than those without emphysema in this study. CONCLUSIONS: This study revealed eight risk factors for fatal AEIP.

[Surgical Treatment of T3 Lung Cancer with Invasion of Chest Wall and Other Adjacent Organs].

We conducted a retrospective investigation in patients who underwent surgery for T3 lung cancer with invasion of chest wall and other adjacent organs. Fifty patients who underwent surgery for T3 lung cancer with invasion of adjacent organs were investigated. The chest wall was the most frequently invaded organ, followed by the pericardium and mediastinal pleura. In cases of chest wall invasion, patients underwent en bloc resection and, when a complete resection was judged feasible, extrapleural resection. Six patients with superior sulcus tumor underwent surgery after preoperative treatment. The 5-year-survival was 55.7%. A significant difference in 5-year survival was observed between complete resection and incomplete resection in patients with lung cancer with chest wall invasion( p<0.047).

Effects of bone marrow and hepatocyte transplantation on liver injury.

BACKGROUND: The therapeutic effects of bone marrow and hepatocyte transplantation were investigated regarding the treatment of retrorsine-partial hepatectomy-induced liver injury. METHODS: Analbuminemic F344alb rats were given two doses of retrorsine 2 wk apart, followed 4 wk later by transplantation with F344 rat bone marrow cells or hepatocytes immediately after a two-thirds hepatectomy. The survival rate, liver regeneration rate, liver functions, albumin-positive hepatocytes, and normal albumin gene sequences in the liver and serum albumin levels were investigated in the recipients. RESULTS: Although 65% retrorsine/partial hepatectomy-treated F344alb died between 1 and 11 d after the partial hepatectomy, only 27.5% of the animals died following bone marrow transplantation, and 50% with hepatocyte transplantation. Both bone marrow and hepatocyte transplantation ameliorated acute liver injury after a partial hepatectomy. Bone marrow transplantation yielded a very small increase in the number of albumin-positive hepatocytes in the liver, while hepatocyte transplantation resulted in massive replacement of the liver tissues by the donor hepatocytes associated with an elevation of serum albumin after an extended time. CONCLUSIONS: Both bone marrow and hepatocyte transplantation could prevent acute hepatic injury, conceivably due to a paracrine mechanism.

Visceral subpleural hematoma of the left diaphragmatic surface following left upper division segmentectomy.

BACKGROUND: Pulmonary visceral subpleural hematoma is rare. We report visceral subpleural hematoma of the left diaphragmatic surface following left upper division segmentectomy. This very rare case was difficult to distinguish from thoracic abscess. CASE PRESENTATION: A 68-year-old man with hypertension had undergone video-assisted thoracoscopic left upper division segmentectomy for suspected lung carcinoma. Deep vein thrombosis of the lower leg was identified and edoxaban, a so-called novel oral anticoagulant, was started on postoperative day 7. The chest drainage tube was removed on postoperative day 12 because of persistent air leakage, but fever appeared the same day. Computed tomography revealed a cavity with mixed air and fluid, so antibiotics were started on suspicion of abscess. Computed tomography-guided drainage was attempted, but proved unsuccessful. Fever continued and surgical investigation was therefore performed. Visceral subpleural hematoma was identified under the diaphragmatic surface of the left basal lung. We excised the pleura, then performed drainage and applied running sutures. The parenchyma and visceral pleura were covered with polyglycolic acid sheet and fibrin glue. Edoxaban was restarted on postoperative day 12 of video-assisted thoracoscopic surgery and no recurrence of hematoma has been revealed. CONCLUSIONS: Visceral subpleural hematoma after thoracic surgery is extremely rare. Furthermore, correct diagnosis was difficult and surgery offered a good diagnostic and therapeutic procedure.

Long-Term Outcomes after Video-Assisted Thoracoscopic Pericardiectomy for Pericardial Effusion.

PURPOSE: Chronic or recurrent pericardial effusion is often associated with malignant disease. However, there have been few reports of the long-term outcomes after video-assisted thoracoscopic (VATS) pericardiectomy. We have performed it since 1992, and report our procedure and outcomes. METHODS: Patients who underwent VATS pericardiectomy were investigated. RESULTS: In all, 29 patients (12 men; median age: 61 (23-88) years) were evaluated; 8 had no malignancies and 21 did. Preoperative performance status (PS) scores were as follows: 1, 11 patients; 2, 10 patients; 3, 5 patients; and 4, 2 patients. One patient with malignancy died intraoperatively. PS improved significantly after the procedure (p = 0.0163). Median survival times were 5360 days in the nonmalignant group, 160 days in the malignant group, 209 days in breast cancer patients, and 62 days in other malignancy patients. The nonmalignant group had significantly longer survival than the malignant group (p = 0.0015). Most cases had uneventful postoperative courses. No recurrent pericardial effusions have been observed. CONCLUSION: In cases of nonmalignant pericardial effusion, long-term survival is expected following VATS pericardiectomy. Malignant pericardial effusion has a poor prognosis, but most cases maintain good PS. However, early postoperative death may occur, and it is important to select patients carefully.

F344 rat liver nonparenchymal cell transplantation can increase the number of albumin-positive hepatocytes in the liver following hematopoietic reconstitution in irradiated analbuminemic rats.

The adult liver contains hematopoietic stem cells that can reconstitute the bone marrow. We tested whether bone marrow cells (BMCs) derived from liver nonparenchymal cells (LNPCs) can increase the number of hepatocytes within livers. LNPCs from Fischer 344 rats (F344) were infused into the penile veins of F344 congenic Nagase's analbuminenic rats (F344alb) immediately after whole-body irradiation, and the recipients were sacrificed 8 weeks later. Eleven of 15 (73.3%) F344alb that received the LNPC transplantation after irradiation survived, while only 1 of 8 (12.5%) F344alb that received irradiation alone was alive after 8 weeks. Normal albumin gene sequences were detected by PCR in BMCs of the recipient F344alb that received LNPC transplantation after irradiation, indicating that F344alb bone marrow was reconstituted by F344 LNPCs. Although single or pairs of albumin-positive (Alb+) hepatocytes were seen in the liver of untreated F344alb and those with irradiation or LNPC transplantation alone, clusters consisting of >3 Alb+ hepatocytes were detected in the livers of F344alb with the LNPC or BMC transplantation after irradiation together with single or double Alb+ cells. Normal albumin gene sequences were detected by PCR in the DNA isolated from such Alb+ hepatocyte clusters microdissected from the immunostained sections. The data indicate that BMCs derived from F344 LNPCs could increase the number Alb+ hepatocytes within the F344alb liver.

Albumin-producing hepatocytes derived from cryopreserved F344 rat bone marrow cells transplanted in the livers of congenic Nagase's analbuminemic rats.

PURPOSE: Hematopoietic stem cells (SCs) are thought to have the potential to differentiate into hepatocytes; however, this potential has not been reported for cryopreserved SCs. We investigated whether cryopreserved bone marrow cells (BMCs) from F344 rats (F344) can induce the growth of albumin-producing hepatocytes in the livers of congenic Nagase's analbuminemic rats (F344alb). METHODS: F344 BMCs were cryopreserved in University of Wisconsin (UW) solution containing 10% fetal bovine serum and 12% dimethylsulfoxide, at -80 degrees C. After thawing, 20 x 10(6) cells were infused via the portal vein into the livers of F344alb immediately after 70% hepatectomy (PH). We examined the recipient livers for albumin-positive (alb+) hepatocytes and albumin mRNA, and measured the serum albumin levels 4 weeks later. RESULTS: Single and double alb+ hepatocytes were occasionally seen in the F344alb livers without the BMC transplantation. However, clusters consisting of more than three alb+ hepatocytes were seen in the livers of recipients transplanted with the cryopreserved BMCs after PH, the same as in the livers transplanted with freshly isolated BMCs. Normal albumin mRNA was detected in the recipient livers and the serum albumin levels were increased. CONCLUSION: Cryopreserved F344 BMCs can induce the growth of alb+ hepatocytes after transplantion in the F344alb liver after PH.

Hepatocytes derived from peripheral blood stem cells of granulocyte-colony stimulating factor treated F344 rats in analbuminemic rat livers.

BACKGROUND: hematopoietic stem cells (SCs) mobilized from the bone marrow (BM) into peripheral blood (PB) are reported to have ability to differentiate into various cell types. We investigated whether PB-SCs mobilized by treatment with granulocyte-colony stimulating factor (G-CSF) in normal rats can raise albumin-producing hepatocytes after transplantation within the liver of analbuminemic rats. MATERIALS AND METHODS: Fischer 344 rats (F344) were used as donors, and F344 congenic Nagase's analbuminemic rats (F344alb) as recipients. The donors were repeatedly treated with human recombinant G-CSF, and their PB mononuclear cells (MNCs) were infused into the portal veins of recipients immediately after 70% hepatectomy (PH). RESULTS: Although a few single and small clusters (less than five cells) of albumin positive (alb+) hepatocytes were seen in the livers of untreated F344alb and of the animals undergoing PH alone or transplantation of PB-MNCs with or without the prior G-CSF treatment, clusters consisting of more than 6 alb+ hepatocytes were only detected in the livers of recipients that received transplantation of mobilized PB-MNCs or BM-MNCs under the regenerating condition induced by PH. Sry3, a Y chromosome marker, could be detected corresponding to the alb+ clusters by in situ hybridization when male donors and female recipients were used. Moreover, normal albumin gene sequences were demonstrated in the microdissected alb+ clusters by polymerase chain reaction, and the serum albumin levels were elevated in the recipients. CONCLUSIONS: Hematopoietic SCs mobilized from BM into PB by the G-CSF treatment may raise hepatocyte colonies, when transplanted into regenerating livers.

Colonization of albumin-producing hepatocytes derived from transplanted F344 rat bone marrow cells in the liver of congenic Nagase's analbuminemic rats.

BACKGROUND/AIMS: We investigated whether bone marrow cells (BMCs) of normal rats can be transformed in albumin-producing hepatocytes in analbuminemic rat livers. METHODS: BMCs (2 x 10(7)) from F344 rats (F344) were infused via the portal vein into the livers of congenic Nagase's analbuminemic rats (F344alb) immediately after 70% hepatectomy (PH). Alternatively, F344alb were hematopoietically reconstituted with F344 BMCs by whole body irradiation and BMC transplantation before PH. The recipients were examined for albumin positive (alb +) hepatocytes and albumin mRNA in the livers as well as serum albumin levels 4 weeks later. Sry3 in situ hybridization was done for the livers of female F344alb that received male F344 BMCs. RESULTS: Livers of untreated F344alb contained a few single and double alb+hepatocytes, but these did not form clusters after PH. Clusters (>3 alb + hepatocytes) were detected in livers of the recipients which were transplanted with BMCs immediately after PH as well as the reconstituted F344alb with or without PH. Normal albumin mRNA was detected in the recipient livers, and serum albumin levels were increased. Sry3 was identified in the alb+clusters in the female recipients. CONCLUSIONS: Transplanted BMCs from normal rats can increase clusters of albumin-producing hepatocytes within the liver of analbuminemic rats.

UW solution: a promising tool for cryopreservation of primarily isolated rat hepatocytes.

Cryopreserved hepatocytes are a ready source of metabolic and synthetic functions for hepatocyte transplantation and bioartificial livers. In this study, we evaluated a cytoprotective effect of University of Wisconsin (UW) solution during cryopreservation of rat hepatocytes. We also investigated the feasibility of lentivirus-based gene transfer into thawed hepatocytes after cryopreservation. Primary rat hepatocytes were isolated using a two-step collagenase perfusion technique, and the resulting hepatocytes with more than 85% viability assessed by a trypan blue exclusion test were subjected to the present study. These cells were subjected to the present study. Cells were cryopreserved with UW solution containing 10% fetal bovine serum (FBS) with 12% dimethylsulfoxide (DMSO) (group 1, G1), Cellbanker solution (group 2, G2), and 10% FBS-containing Dulbecco modified Eagle medium (DMEM) with 12% DMSO (group 3, G3). After thawing the cryopreserved hepatocytes, cell viability, plating efficiency, morphological appearance, and ammonia clearance activity were determined for each group. The efficacy of lentivirus-mediated Escherichia coli LacZ gene delivery was evaluated. Hepatocyte viabilities after 3- and 7-day cryopreservation were 73.2% and 62.5% for G1, 57.5% and 46.5% for G2, and 57.3% and 41.5% for G3, respectively. Plating efficiency and ammonia clearance activity were improved in G1 hepatocytes compared to G2 and G3 cells. Lentiviral transfer of a LacZ gene was confirmed in the thawed hepatocytes after cryopreservation by an X-gal stain assay.