Sustained-Release Tacrolimus Stabilizes Decline of Forced Expiratory Volume in 1 Second Through Decreasing Fluctuation of Its Trough Blood Level.

BACKGROUND: Calcineurin inhibitors are a commonly used immunosuppressive drug and over 80% of lung transplant (LTx) recipients use tacrolimus. Sustained-release tacrolimus (SRT) was developed as a once-daily formulation, resulting in slower release and reduction in peak concentration compared with twice-daily immediate-release tacrolimus (IRT). Previous reports indicate that SRT may carry fewer side effects than IRT; however, the impact of SRT in bronchiolitis obliterans syndrome (BOS) after LTx is unclear. OBJECTIVE: Our study objective was to evaluate the effect of SRT in BOS after LTx. MATERIALS AND METHODS: We investigated the effect of SRT for BOS among 75 LTx recipients who were alive in 2017 in our LTx program. All analyses were carried out using student t test or F test. RESULTS: Thirty-five recipients took IRT, 32 recipients used SRT, 7 recipients used cyclosporine, and 1 patient who received bone marrow and a lung graft from the same donor did not use a calcineurin inhibitor. The most frequent reason for conversion of IRT to SRT was kidney dysfunction, followed by other IRT complications. Five recipients underwent conversion of IRT to SRT because of decline of forced expiratory volume in 1 second (FEV1) with fluctuation of the tacrolimus trough level. After induction of SRT, the fluctuation of the tacrolimus trough level was significantly reduced in 4 of 5 patients (P < .05). Before drug form conversion, the FEV1 in these 5 patients was significantly decreased; however, this exacerbation of FEV1 was attenuated after SRT induction (P < .05). CONCLUSION: SRT appeared to stabilize decline of FEV1 in patients with BOS possibly due to reducing the fluctuation of tacrolimus trough blood concentration.

Endobronchial Topical Amphotericin B Instillation for Pulmonary Chromomycosis After Lung Transplantation: A Case Report.

We report a very rare case of pulmonary chromomycosis caused by Scedosporium prolificans that developed after lung transplantation and was successfully treated with endobronchial topical amphotericin B instillation. The subject was a woman in her 50s with a history of bilateral lobar lung transplantation from living donors for idiopathic pulmonary hypertension. Eight years after the lung transplantation, chest radiography X-ray and computed tomography showed an abnormal shadow in the right lung. Bronchoscopic findings showed obstruction by a fungal component at the laterobasal bronchus B9. She was diagnosed with pulmonary chromomycosis after S. prolificans was detected in the bronchial aspirate. Systemic antifungal treatment with itraconazole was ineffective. Therefore, we administered topical amphotericin B weekly via endobronchial instillation and replaced oral itraconazole with voriconazole. The endobronchial procedure was safe and tolerable. Bronchial obstruction improved after three 3 instillations. We continued topical amphotericin B instillation once every 3 months for 2 years, and the abnormal shadow nearly disappeared. This case report describes infection by S. prolificans, which rarely becomes an etiologic agent in lung transplant patients, and shows that endobronchial topical amphotericin B instillation is a therapeutic option when systemic antifungal treatment is ineffective.

Prolonged Negative Pressure Wound Therapy Followed by Split-Thickness Skin Graft Placement for Wide Dehiscence of Clamshell Incision After Bilateral Lung Transplantation: A Case Report.

Clamshell incision is a standard approach for bilateral lung transplantation, providing a good operative field; however, once wide dehiscence occurs, its management is sometimes difficult because of intense immunosuppression and malnutrition of the recipient. A 22-year-old man with idiopathic pulmonary arterial hypertension underwent cadaveric bilateral lung transplantation through a clamshell incision using standard cardiopulmonary bypass. He developed wound dehiscence on postoperative day (POD) 20 that resulted in exposure of the bilateral fifth ribs and open pneumothorax. Considering the extreme malnutrition and emaciation of the recipient, we avoided initial closure of the dehiscence. After the debridement of necrotic tissue, negative pressure wound therapy was initiated on POD 25 and was continued for approximately 6 months with trafermin spray application. Eventually, the wound, including the fifth ribs, was completely covered with granulation tissue except for the wire tying the sternum. On POD 217, the patient underwent removal of the sternal wire followed by split-thickness skin grafting. His wound was successfully closed and he was discharged without activity limitation on POD 265.

Medical consultant system for improving lung transplantation opportunities and outcomes in Japan.

Because the shortage of donor organs is especially serious in Japan, since 2002 a unique partnership between transplant consultant physicians and local physicians has been developed to maximize the organ utilization rate. Since 2011, more than 25 lung consultant physicians have been registered to specifically assess donor lungs and provide advice on intensive respiratory care to donors. In this study, we retrospectively reviewed the efficacy of this system for lung transplantation opportunities and outcomes. One hundred eighty-seven brain-dead lung donor candidates were chronologically divided into 3 phases: I (May 1998-November 2006) and II (December 2006-January 2011), before and after medical consultants requested that local physicians administer aggressive bronchial suctioning using bronchoscopy, respectively; and phase III (February 2011-January 2013), after the emergence of lung consultants. The lung utilization rate, Pao2/Fio2 ratio at the first and second brain death examinations and at the tertiary assessment before recovery, and graft survival were analyzed. The lung utilization rate was significantly higher in phases II and III than in phase I. In phases I and II, the Pao2/Fio2 ratio at the tertiary assessment was significantly lower than that at the first or the second brain death examination, whereas it did not worsen with time in phase III. Graft survival was significantly better in phases II and III than in phase I. Graft death due to primary graft dysfunction was significantly more frequent in phase I than in phases II and III. In conclusion, this system is effective in improving lung transplantation opportunities and outcomes.

Steroid sulphatase and oestrogen sulphotransferase in human non-small-cell lung carcinoma.

BACKGROUND: Steroid sulphatase (STS) is one of the steroid-metabolising enzymes involved in desulphating inactive steroid sulphates and oestrogen sulphotransferase (EST) sulphates active oestrogen. The roles of both STS and EST have not been examined in oestrogen-dependent non-small-cell lung cancer (NSCLC). METHODS: We evaluated the immunoreactivity of STS and EST in NSCLC cases using immunohistochemistry. The function of STS and EST was further demonstrated using NSCLC cell lines. RESULTS: The immunoreactivity of STS and EST was detected in 49.5% and 27.8% of NSCLC cases, respectively. The immunoreactivity of STS was significantly higher in female adenocarcinoma cases. The STS-positive NSCLCs were also significantly correlated in an inversed manner with tumour size and cell proliferation and tended to be associated with better clinical outcome. However, the immunoreactivity of EST was significantly correlated with intracellular oestradiol concentration. Results of in vitro analysis demonstrated that oestrone sulphate (E1-S) induced and pregnenolone sulphate (Preg-S) inhibited the proliferation in STS-expressing cell lines. The inhibition by Preg-S was reversed by a specific progesterone receptor blocker. Simultaneous addition of E1-S and Preg-S significantly suppressed the proliferation. CONCLUSION: In NSCLC patients, STS is considered a good prognostic factor. Results of our present study also indicated the benefits of potential progesterone therapy for NSCLC patients.

[Radical surgery using modified open door method for anterior apical tumor].

The approach that should be used for an anterior apical tumor still remains controversial. Since a modified open door method was very useful for the widening of the surgical field in a recent patient with an anterior apical tumor, an outline of this case is reported. The patient was a 66-year-old male with squamous cell carcinoma of the anterior apical region of the right lung (suspected to be invading the thoracic wall, cT3N1M0). After a midline sternal incision with a right unilateral collar incision, the medial half of the right clavicle and a few cm of the right 1st rib on the sternal side were resected to sufficiently expose the area from the right brachiocephalic trunk to around the subclavicular artery and vein, where invasion was suspected. This treatment facilitated widening of the visual field around the site of tumor invasion and made safe right upper lobectomy + combined thoracic wall resection + ND2a possible. In this patient, anterolateral incision at the 4th intercostal level, which is made using the original open door method, could be avoided, probably minimizing surgical invasion.

[Problems in donor lung evaluation for transplantation with regard to airway infection].

The shortage of donor organs has been 1 of the major obstacles to solid organ transplantation. Typical lung donor criteria include clear lung field on chest radiograph, adequate oxygenation, acceptable lung compliance, and satisfactory bronchoscopic findings. To extend usage of available donors, liberalization of donor lung selection criteria has been facilitated, however, marginal donor lungs must be used with discretion, because donor lung injury, especially that related to infection, has a potential leading to early post-operative death of the recipient. From March 2000 to December 2006, we evaluated 15 braindead donors and at least 1 of the lungs from 9 donors was judged suitable for transplantation. One of 9 recipients developed severe pneumonia cased by carbapenems-resistant Pseudomonas aeruginosa possibly originating from the donor lungs, eventually leading to death. The chest radiograph and oxygenation of the donor had been satisfactory, however, a moderate amount of mucopurulent secretions was observed by bronchoscopic inspection and the donor had been given a cefozopran for 9 days before the procurement operation. Remaining 8 recipients were free from air-way infection in the early postoperative period. We discuss the status and problems of donor lung evaluation for transplantation with regard to donor lung infection.

Dementia in Parkinson's disease: diffusion tensor imaging.

OBJECTIVE: Dementia occurs frequently in patients with Parkinson's disease (PD). However, the nature of the dementing process remains controversial. We evaluated various cognitive functions in patients with PD, compared fractional anisotropy (FA) values between PD patients with and without dementia. METHODS: Thirty-seven consecutive patients with Hoehn-Yahr stage III or IV PD participated in this study. Patients were divided into two groups: (i) PD with dementia group (PDD) and (ii) PD without dementia group (PDND). There were 11 PDD and 26 PDND cases. Ten controls were also studied. RESULTS: The PDD group showed significant FA reduction in the bilateral posterior cingulate bundles compared with PDND. FA values in the left posterior cingulate bundle showed significant correlations with many cognitive parameters. INTERPRETATION: Our results showed that the posterior cingulate areas play some important roles in the dementing process in PDD. However, as the pathological processes responsible for dementia in PD patients may be multifaceted, further studies are necessary.

Wisconsin Card Sorting Test in Parkinson's disease: diffusion tensor imaging.

INTRODUCTION: It is generally assumed that executive dysfunctions in Parkinson's disease (PD) are caused by degeneration of the basal ganglia or frontal cortex or both. However, there have been few studies investigating the relationship between executive dysfunctions and cerebral pathological change. The objective of this study was to evaluate various cognitive functions in non-demented patients with PD, and to compare the fractional anisotropy (FA) values of PD patients with and without executive dysfunction. MATERIALS AND METHODS: Twenty-one consecutive non-demented patients with PD were enrolled in this study. Patients were divided into two groups on the basis of their Wisconsin Card Sorting Test score. RESULTS: There was significant FA reduction in the left parietal white matter in the group in which the number of categories achieved was 2. CONCLUSION: Accumulating evidence suggests that conventional 'frontal' tasks correlate with both frontal lobe and parietal lobe function, and we suggest that pathological changes in the left parietal lobe may cause, in part, disturbances in executive tasks in PD.

[Primary lung cancer incidentally diagnosed in lung biopsy for diffuse pulmonary disease].

UNLABELLED: We here presented 2 cases of interstitial pneumonia with lung adenocarcinoma incidentally diagnosed by partially resected lung for diffuse pulmonary disease. CASE 1: A 78-year-old female was admitted to the hospital complaining of productive cough and general fatigue. The chest computed tomography (CT) revealed diffuse honey comb pattern in bilateral lung field especially in the right lower lung. Video-assisted thoracoscopic lung biopsy was performed and was diagnosed as diffuse spreading well differentiated adenocarcinoma. CASE 2: A 59-year-old male was admitted to the hospital complaining of dyspnea and general fatigue. The chest X-ray revealed right pneumothorax and chest CT revealed diffuse honey comb pattern and bullae in bilateral lung field and fibrous tumor-like lesion in the right middle lung. Video-assisted thoracoscopic lung biopsy was performed and was diagnosed as pulmonary fibrosis with papillary adenocarcinoma. CONCLUSION: It is important to examine carefully the specimen obtained from thoracoscopic lung biopsy even if interstitial pneumonia is strongly suspected.

[Spontaneous regression of thymoma; report of a case].

A 44-year-old woman was admitted to our hospital with chest pain. Chest roentgenograms and computed tomography (CT) scan revealed an anterior mediastinal tumor and bilateral pleural effusion. However, CT scan 3 days after magnetic resonance imaging (MRI) revealed regression of the tumor. Extended thymo-thymectomy was performed via median sternotomy. The tumor was in the right lobe of the thymus. Pathologically the tumor was diagnosed as a mixed type non-invasive thymoma, but some parts of the tumor cells were necrotic. This is the 10th case of spontaneous regression of thymoma reported in the Japanese literature.

[Radiofrequency ablation for metastatic lung tumor].

BACKGROUND: Radiofrequency ablation (RFA) is a thermal ablation technique which results in coagulative necrosis. Several preliminary studies have evaluated the efficacy of RFA for liver tumor and benign prostate disease, but few studies for lung tumor. We experienced RFA for a metastatic lung tumor and it was effective. CASE: A 61-year-old woman was admitted to our hospital with chest pain. Extended thymothymomectomy with lymph node dissection was performed after diagnosis of thymic carcinoid. After 14 months, multiple small lung nodules, which had been 5-10 mm in diameter, were appeared and resected. However, 23 months after the first operation and 14 months after the second operation, multiple small lung nodules were appeared again and RFA was performed for 1 tumor without any complications. We used RITA 500 PA (RITA Medical Systems, INC.) and quadruple-hook radiofrequency probe with electrodes. Under local anaesthesia and ultrasound guidance, the probe was inserted into the target tumor and the hooks were deployed. The tumor became smaller (35 mm to 25 mm in diameter) in 2 months. CONCLUSION: RFA is an effective and minimally invasive technique to destruct local tumors.