Hyperinflation With Pulmonary Dysfunction in Donor Lungs With Smoking History During Lung Perfusion.

BACKGROUND: Donor lungs with smoking history are perfused in ex vivo lung perfusion (EVLP) to expand donor lung pool. However, the impact of hyperinflation of perfused lungs in EVLP remains unknown. The aim of this study was to investigate the significance of hyperinflation, using an ex vivo measurement delta VT, during EVLP in smoker's lungs. MATERIALS AND METHODS: Seventeen rejected donor lungs with smoking history of median 10 pack-years were perfused for 2 h in cellular EVLP. Hyperinflation was evaluated by measuring delta VT = inspiratory - expiratory tidal volume (VT) difference at 1 h. All lungs were divided into two groups; negative delta VT (n = 11, no air-trapping pattern) and positive delta VT (n = 6, air-trapping pattern). Transplant suitability was judged at 2 h. By using lung tissue, linear intercept analysis was performed to evaluate the degree of hyperinflation. RESULTS: The positive delta VT group had significantly lower transplant suitability than the negative delta VT group (16 versus 81%, P = 0.035). The positive delta VT group was significantly associated with lower partial pressure of oxygen/fraction of inspired oxygen ratio ratio (278 versus 356 mm Hg, P = 0.049), higher static compliance (119 versus 98 mL/cm H2O, P = 0.050), higher lung weight ratio (1.10 versus 0.96, P = 0.014), and higher linear intercept ratio (1.52 versus 0.93, P = 0.005) than the negative delta VT group. CONCLUSIONS: Positive delta VT appears as an ex vivo marker of ventilator-associated lung hyperinflation of smoker's lungs during EVLP.

Plasma mycophenolic acid concentration and the clinical outcome after lung transplantation.

BACKGROUND: The therapeutic drug monitoring of mycophenolic acid (MPA) has been investigated for renal and heart transplantations; however, its usefulness in lung transplantation is unclear. METHODS: The MPA area under the plasma concentration-time curve (AUC) was calculated in 59 adult lung transplant recipients. The MPA AUC0-12 s were compared among the three groups determined by the presence of adverse events (no events, infection, and chronic lung allograft dysfunction [CLAD]). Next, MPA AUC0-12 thresholds for the adverse events were identified by receiver operating characteristic analysis. Cumulative occurrence rate of the adverse events was compared between two groups (adequate and inadequate groups) according to the thresholds. RESULTS: The MPA AUC0-12 s in the no event, infection, and CLAD groups were 30.3 ± 6.5, 36.8 ± 10.7, and 20.6 ± 9.6 µg·h/mL, respectively (P = .0027), while the tacrolimus trough levels were similarly controlled in the groups. The thresholds of MPA AUC0-12 for the occurrence of infection and CLAD were 40.5 and 22.8 µg·h/mL, respectively. The cumulative occurrence rate of adverse events of adequate group (15.3%) was significantly lower than that of inadequate group (56.0%) (P = .0050). CONCLUSIONS: The MPA AUC0-12 may affect the occurrence of adverse events in lung transplant recipients.

Muse Cells and Ischemia-Reperfusion Lung Injury.

Ischemia-reperfusion injury (IRI) is one of the main causes of primary graft dysfunction that accounts for 25% of mortality after lung transplantation. Disruption of blood supply and subsequent reperfusion result in organ damage with activating innate and adaptive immune response, leading to inflammatory insults. The IRI after lung transplantation is primarily manifested by permeability pulmonary edema on the basis of pulmonary vascular endothelial cell injury as seen in acute respiratory distress syndrome (ARDS). Stem cells have potent anti-inflammatory and immunomodulatory properties through local paracrine mechanisms. The application of mesenchymal stem cells (MSCs) for ARDS as well as IRI in various organs, therefore, has been interested and extensively investigated in animal models with promising results. Furthermore, two recent clinical randomized, placebo-controlled pilot studies demonstrated that treatment of ARDS with MSCs appears to be safe and feasible.Muse cells are stress-tolerant and non-tumorigenic endogenous pluripotent-like stem cells. They comprise small proportions of cultured fibroblasts and MSCs and can be isolated from these populations. Muse cells are known to migrate to the damaged tissue after local or systemic administration, spontaneously differentiate into the tissue-compatible cells, and also secrete factors related to immunomodulation and tissue repair. We have recently shown the effect of Muse cells on ameliorating lung IRI in a rat model. With 2 h of warm ischemia and subsequent reperfusion on the left lung, the lung showed severe pulmonary edema. Administration of Muse cell through the left pulmonary artery immediately after reperfusion more significantly improved lung oxygenation capacity, compliance, and histological damage on days 1 and 3 after reperfusion compared with MSCs, and this was associated with higher expression levels of proteins related with anti-inflammation and tissue repair in the lung. Encouraging results of this study advocate further investigation of the ability of Muse cells to prevent and treat IRI after lung transplantation.

Influences of environmental noise level and respiration rate on the accuracy of acoustic respiration rate monitoring.

We tested the hypothesis that the environmental noise generated by a forced-air warming system reduces the monitoring accuracy of acoustic respiration rate (RRa). Noise levels were adjusted to 45-55, 56-65, 66-75, and 76-85 dB. Healthy participants breathed at set respiration rates (RRset) of 6, 12, and 30/min. Under each noise level at each RRset, the respiration rates by manual counting (RRm) and RRa were recorded. Any appearance of the alarm display on the RRa monitor was also recorded. Each RRm of all participants agreed with each RRset at each noise level. At 45-55 dB noise, the RRa of 13, 17, and 17 participants agreed with RRset of 6, 12, and 30/min, respectively. The RRa of 14, 17, and 16 participants at 56-65 dB noise, agreed with RRset of 6, 12, and 30/min, respectively. At 66-75 dB noise, the RRa of 9, 15, and 16 participants agreed with RRset of 6, 12, and 30/min, respectively. The RRa of one, nine, and nine participants at 76-85 dB noise agreed with RRset of 6, 12, and 30/min, respectively, which was significantly less than the other noise levels (P < 0.05). Overall, 72.9% of alarm displays highlighted incorrect values of RRa. In a noisy situation involving the operation of a forced-air warming system, the acoustic respiration monitoring should be used carefully especially in patients with a low respiration rate.

[Anomalous systemic arterial supply to left basal lung with anomalous return of V6].

The patient was 52-year-old woman. Her chief compliant was bloody sputum. The computed tomography revealed an anomalous artery from descending aorta running into left lung basal segment and anomalous left V6 return to superior pulmonary vein. The bronchoscopic examination showed normal bronchial branches. Under the diagnosis of anomalous systemic arterial supply to left basal lung without sequestration, left lower lobectomy was performed. Microscopically, the pulmonary artery showed intimal thickening and alveolar collapse with interstitial fibrosis were seen. The postoperative course was uneventful and she discharged at 6th postoperative day.

[Heparin-induced thrombocytopenia developed during the acute phase after left upper lobectomy for lung cancer].

Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin administration. This must not be rarely encountered but is not often reported in Japan compared to Western countries. A 68-year-old woman underwent left upper lobectomy for lung cancer. Low-dose unfractionated heparin was administrated to prevent thromboembolism after the operation. Two days later, sudden dyspnea appeared and ultracardiosonography showing an extensive thromboembolus from the main trunk to both main branches of pulmonary artery indicated pulmonary embolization. After the establishment of percutaneous cardiopulmonary support (PCPS) support, the embolus was removed by emergent open heart surgery. However, despite further unfractionated heparin administration following embolization surgery, other thrombus was identified in both the bi-lateral internal jagular veins and inferior vena cava by ultrasonography and contrast computed tomography( CT). Her platelet count was decreased gradually despite platelet transfusion. Plate factor 4( PF4) antibody against heparin in her blood examination was found, and HIT II was diagnosed. Discontinuation of unfractionated heparin and administration of antithrombin agent improved platelet count, and no additional embolization was identified.

[Empyema that was diagnosed as primary ciliary dyskinesia by electron microscopical image of nasal mucosa].

A patient was 17-year-old. She had a history of repeated pneumonia and sinusitis. She was admitted to our hospital with the diagnosis of pneumonia. Although she was prescribed a course of antibiotics, chest roentgenogram and computed tomography showed increased and capselized pleural effusion, suggesting the development of acute empyema. Capsulized effusion and pus in thorax were removed by surgery. A part of lingular segment was raptured necessitating the partial resection of lingular segment. Her postoperative course was well. Her history of repeated pneumonia and sinusitis indicated the existence of primary ciliary dyskinesia, and the biopsy of nasal mucosa was done. The electron microscopical image of nasal mucosa showed defect of inner dynein arm. We made a diagnosis of primary ciliary dyskinesia based on her previous history and electron microscopical image.

[Primary malignant peripheral nerve sheath tumor of the lung; report of a case].

We report a patient with primary malignant peripheral nerve sheath tumor (MPNST) of the lung. A 84-year-old man was referred to our hospital because of an abnormal shadow on chest X-ray. The computed tomography( CT) of the chest revealed a 6 cm tumor close to the posterior chest wall in the left thorax. He was followed-up because a benign tumor from posterior mediastinum was suspected. But the CT after 17 months showed the tumor enlargement. We performed complete resection under video-assisted thoracic surgery. It arose from the left lower lobe and was diagnosed as primary MPNST of the lung by immuno-histopathological examination. MPNSTs have a poor prognosis with tendency to recur. Although there is no sign of recurrence a year after surgery, we should follow-up carefully.

[The influence of difference of surgical procedure for the young spontaneous pneumothorax to the recurrence rate after surgery].

INTRODUCTION: In spontaneous pneumothorax (SP) in patients under the age of 30, we studied the postoperative recurrence rate due to differences in the surgical procedures and the patient's age. MATERIALS AND METHODS: Between October 2003 and September 2012, 351 operations were performed for the young(30 years or younger)SP in our hospital. The recurrence rate was calculated in 2 age groups( under 20 or older) with different surgical procedures which were classified into 5 groups on the basis of the combination of the covering site with the polyglycol acid (PGA) seat and the presence or absence of ligation at both ends of staple-line. RESULTS: The mean age of all patients was 21.0±4.4, 320 were male. The recurrence rate of all was 8.8%.The group 20 years or younger in comparison with the group 21 years or older had significantly high recurrence rate after surgery(11.9% v.s. 5.1%;p=0.034).However, covering the staple-line with ligation of both ends and covering the staple-line and the bullae common site were both significantly lower recurrence rate compared with the group with covering only to the staple-line in 20 years or younger group(0% v.s. 23.8%;p=0.041, 4.9% v.s. 23.8%;p=0.041). CONCLUSION: The results suggest that we need to choose the appropriate procedure of the surgery for SP considering the patient's age. The recurrence rate in the patient 20 years or younger can be reduced by covering the bullae common site and/or the ligating both ends of staple-line in addition to covering the staple-line.

[Mixed squamous and glandular papilloma].

The patient was a 64-year-old man. He had a smoking history for 43 years (20 cigarettes per day). Being pointed out a mass shadow in the left lower lung field on chest X-ray in a regular checkup, he was referred to our hospital. The chest computed tomography (CT) revealed a tumor shadow of 30 mm diameter in the left S8. Blood tests showed that carcinoembryonic antigen (CEA) and squamous cell carcinoma-related antigen (SCC) were elevated. Accumulation of standardized uptake value (SUV) max 9.78/15.17 match the tumor shadow in fluorodeoxyglucose positron emission tomography (FDGPET),suspected of malignancy. As a result of bronchoscopy, squamous cell carcinoma was suspected by cytology, and he was introduced to us for surgery. Video-assisted thoracic surgery (VATS)-left lower lobectomy and lymph node dissection was performed. By pathology, the tumor showed papillary growth in peripheral bronchus, with squamous cell and high columnar epithelial cell components. The tumor was diagnosed as mixed squamous and glandulas papilloma. In addition, a part of the squamous cells was considered to be atypical, indicating squamous cell carcinoma in situ in a mixed epithelial and glandular papilloma.

[Re-operation for recurrent pulmonary metastases].

Fifty two patients with metastatic lung tumors were treated surgically in our hospital. Second pulmonary resections were performed in 6 patients. They consist of 1 male and 5 females, their age ranged from 59 to 80 years old( average 66 years old). Tumors originate from laryngeal cancer, colorectal cancer in 2 cases respectively, lung cancer and hepatic cancer in 1 case respectively. Three-year and 5-year survival was seen in 75% and 75% of patients, respectively.

[Treament using a free omental flap for pulmonary Aspergillosis with chronic methicillin-resistant Staphylococcus aureus( MRSA) empyema after fenestration].

A case is 48-year-old man who had a history of Blalock-Taussig shunt and the radical operation for Fallot's tetralogy, had been performed cavernostomy and fenestration operation for aspergilloma of left upper lobe in the previous hospital due to control blood spitting. Although the contents of the abscess cavity were removed, the opened cavity was again infected by methicillin-resistant Staphylococcus aureus (MRSA) and he was referred to our hospital. The plombage of free omental flap with vascular anastomosis was performed. He has been well without any symptoms or recurrence of empyema for 6 years after surgery.

[Primary pulmonary malignant melanoma].

The patients was 63-year-old man. He had a chest abnormally shadow pointed out in examination of March, 2012 and referred to our hospital for a close inspection. The chest computed tomography(CT)revealed a mass shadow of 60 mm in left lung. Bronchoscopic examination was done and it was diagnosed as non-small-cell lung cancer by cytology. The clinical stage was cT2bN1M0 and video-assistedthoracic surgery (VATS) left pneumonectomy with mediastinal lymph node dissection was performed. A lot of neoplastic cells which contained melanin in cytoplasm were recognized by pathology and the diagnosis of malignant melanoma was comfirmed. Lymph node metastasis were recognized in #10, #11, #12 and the pathological stage of a disease was pT2bN1M0, pStage IIB. Further examination to find another lesion after surgery was in vain suggesting primary site to be left lung. A adjuvant chemotherapy has not been done. Surgical resection of primary pulmonary malignant melanoma is reported with reference to literatures.

[Schwannoma occurred in the right upper bronchial inlet; report of a case].

A 47-year-old woman was treated at a local hospital for obstructive pneumonia in February 2011. A computed tomography(CT)scan revealed a nodule obstructing the right upper bronchus. Histological diagnosis could not be established by biopsy under the bronchoscopic examination. She was referred to our hospital for further treatment. Since accumulation of fluoro-2-deoxy-D-glucose(FDG)was noted by positron emission tomography(PET)[standardized uptake value(SUV)max 5.67/7.52], primary lung cancer was suspected and right upper sleeve lobectomy was performed. Pathology during surgery suggested the tumor to be schwannoma. Postoperative course was uneventful.

[Examination using multivariate analysis of the risk factors by surgical approach in elderly intractable pneumothorax].

PURPOSE: In this study, we evaluated the risk factors for postoperative complications in elderly patients with intractable pneumothorax and constructed a risk assessment model. MATERIALS AND METHODS: Between January 2004 and December 2011, 83 elderly patients( age, 75 years or older) underwent an operation at our hospital for intractable pneumothorax. Preoperative factors of these cases were assessed to clarify which is contributory to the development of postoperative complications by using univariate analysis and multivariate logistic regression analysis. RESULTS: Thirty-five patients (42.2%) developed postoperative complications. In univariate analysis, total protein, albumin level, blood urea nitrogen, creatinine level, Paco2, body mass index, performance status, and preoperative respiratory complications showed statistically significant associations with the occurrence of postoperative complications. In the multivariate analysis, the performance status showed a statistically significant association( 95% confidence interval, 1.17〜4.44;odds ratio, 2.28;p=0.0157). CONCLUSION: The results suggested that the preoperative examinations were useful in predicting postoperative complications in the elderly patients with intractable pneumothorax. Poor performance status, low nutrition, respiratory failure, and preoperative respiratory complications are risk factors for postoperative complications in elderly patients with intractable pneumothorax.

[A case of colorectal neuroendocrine carcinoma effectively treated with bevacizumab+levofolinate+5-FU chemotherapy].

A 76-year-old woman was admitted to our hospital with diarrhea and weight loss in February 2007. A CT scan revealed a tumor in the abdominal cavity, and although a thorough investigation was conducted, no diagnosis was made. Therefore, she underwent diagnostic surgery in April 2007. Intraoperatively, the tumor was determined to have originated in the transverse colon, with invasion to other organs. The patient underwent a transverse colectomy, partial ileal resection, and partial resection of the bladder and peritoneum were performed. The pathological diagnosis was colorectal neuroendocrine carcinoma. FOLFOX4 chemotherapy was initiated in May 2007. However, a CT scan in June 2007 revealed a recurrent tumor in the right pelvis. Although right hemicolectomy and right oophorectomy were performed in August, a CT scan in September 2007 revealed a recurrent tumor in the right pelvis. Following treatment with bevacizumab+levofolinate+5-FU, the tumor disappeared. The patient continued to receive this chemotherapy regimen until August 2010, and CT scans showed a complete response. Even though colorectal neuroendocrine carcinoma is known to have a poor prognosis, the present case was effectively treated with bevacizumab+levofolinate+5-FU chemotherapy. Herein we provide discussion and suggestions about treatment for colorectal neuroendocrine carcinoma.

[Management of a lung tumor accompanied by aortic dissection; report of a case].

During an annual health check-up, a 75-year-old man was admitted to our hospital due to an abnormal shadow in the left upper lung field. A computed tomography (CT) scan taken at his 1st hospital visit showed a calcified nodule in the left upper lobe and Stanford type A aortic dissection. We could not perform bronchofiberscopy due to the risk associated with the aortic dissection and could not make a diagnosis prior to surgery. Because of the possibility of lung cancer, surgery for the lung tumor and aortic dissection was performed. The pathological diagnosis of the lung tumor was a hematoma. In a case of suspicion of lung cancer along with cardiovascular disease, a surgical diagnosis might be considered.

[Adverse events in patients treated with capecitabine as adjuvant chemotherapy after surgery for colorectal cancer--countermeasures against hand-foot syndrome].

Although the 2009 edition of the Guidelines for Colorectal Cancer Therapy recommend capecitabine as a standard postoperative adjuvant chemotherapy for colorectal cancer therapy, a characteristic adverse event, hand-foot syndrome, develops at a high incidence, and appropriate management is necessary to continue therapy. We investigated countermeasures against adverse events, particularly hand-foot syndrome, in patients treated with capecitabine. The subjects were 47 patients aged 64 years (27-84 years) who underwent surgery for colorectal cancer. They received 8 (2-16) courses of drug administration. No grade 3 blood or non-blood toxicity was noted, and the therapy was relatively safe excluding an enhanced anticoagulant effect. Grade-3 hand-foot syndrome developed in 3 patients, but there were only 10 grade-2/3 cases (21.7%) because humectants and oral vitamin B6 preparation (supportive therapy) were administered from therapy initiation. The incidence increased to 32.6% (15 patients) after June. Symptoms aggravated due to mechanical stimulation of the hands and legs in 5 patients because they were farmers growing cherries, suggesting that investigation of patient living background is also important. The incidence of grade-2/3 hand-foot syndrome was 21.1 and 75% in 39 and 8 patients, respectively, who were treated with supportive therapy from the initiation of drug administration and after several courses of drug administration or development of symptoms. This suggested the usefulness of early supportive therapy. The importance of preventive measures against hand-foot syndrome will increase as capecitabine is increasingly administered. Information exchange between medical staffs and providing patients with appropriate information may lead to management of adverse events and subsequently to continuation and obtaining effects of therapy.

Resecting a giant malignant lung tumor in a patient with unilateral acute interstitial pneumonitis.

Acute interstitial pneumonia is a rare and fulminant form of idiopathic interstitial lung disease. Here, we report a case of a giant malignant sarcomatoid tumor of the left lung with unilateral lung infiltration. The tumor was resected under venovenous extracorporeal membrane oxygenation support. Right middle lung lobe biopsy revealed alveolar epithelial hyperplasia, mild interstitial fibrosis, and interstitial edema. The patient was diagnosed with acute interstitial pneumonitis, and effectively treated with steroid pulse therapy followed by prednisolone. In this case, the contralateral lung expansion accomplished with tumor resection, definitive diagnosis based on lung biopsy, and corticosteroid treatment possibly improved the outcome.

Chest wall/parietal pleural invasions worsen prognosis in T4 non-small cell lung cancer patients after resection.

OBJECTIVES: Appropriate selection for surgery is particularly important in T4 non-small cell lung cancer patients. In clinical settings, patients those who are positive for T4 criteria occasionally are also positive for T3 factors which are independently defined from original T4 or even have multiple T4 factors. Significance of these factors on prognosis is still unknown. METHODS: We retrospectively reviewed clinicopathorogical data of 113 patients with T4 non-small cell lung cancer those who underwent surgery between 1990 and 2015 in Tohoku University Hospital. Significance on prognosis of single or multiple T4 factors and with or without independent T3 factors were statistically analyzed. RESULTS: No significant difference was seen in the 5-year survival rate between patients with single (35.6%) and multiple (31.4%) T4 factors (P = 0.94), but the rate was significantly lower when patients also had independent T3 factors (19.6%) compared with when they did not (42.5%) (P = 0.011). The 5-year survival rate was particularly lower among patients with invasion of the chest wall or parietal pleura (8.1%) than in those without (40.6%) (P = 0.0052). CONCLUSIONS: Invasion of the chest wall or parietal pleura is poor prognostic factors in T4 non-small cell lung cancer patients.