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Neurological paraneoplastic syndrome is a relatively rare condition in patients with malignant tumors. Recently, it has been reported that anti-Aquaporin 4 (AQP4) antibody is highly specific for neuromyelitis optica. The patient was a 76-year-old man. He underwent right upper lobectomy for squamous cell carcinoma of the lung. Although the immediate postoperative course was uneventful, neurological symptoms became apparent from postoperative day (POD) 4. Magnetic resonance imaging showed longitudinally extended edematous lesions in the spinal cord, and a cerebrospinal fluid examination was positive for anti-AQP4 antibody, leading to the diagnosis of paraneoplastic neuromyelitis optica. Despite multiple rounds of steroid pulse therapy and plasma exchange, the neurological symptoms worsened and the patient died on POD 46. The development of neuromyelitis optica in the early postoperative period could be related to the influence of surgical stress or epidural anesthesia.

Infections caused by the Scedosporium genus have become recognized as a fatal complication after lung transplantation in Europe and Australia, but the reports have been rare from Asian countries including Japan. We present a case of pneumonia caused by a mixed infection of Scedosporium apiospermum (SA) and Lomentospora prolificans (LP) that developed after augmentation of immunosuppression for chronic lung allograft dysfunction (CLAD) after lung transplantation. A 13-year-old man underwent bilateral lung transplantation for pulmonary hypertension. One year after surgery, he was treated with a series of augmented immunosuppressive therapy for severe acute rejection and subsequent CLAD. Three months following the first steroid pulse therapy, his serum β-D-glucan elevated without any sign of fungal infection by other tests. The serum β-D-glucan once returned to a normal level by empirical administration of micafungin; however, the patient's condition worsened again by discontinuation of it. He did not recover by restarting micafungin, and computed tomography (CT) scans eventually demonstrated new infiltrates in his lung field 6 weeks after the elevation of serum β-D-glucan. Microscopic findings of transbronchial lung biopsy specimens showed filamentous fungi, and the culture of bronchoalveolar lavage fluid revealed the growth of SA and LP. Despite subsequent voriconazole administration, he died 14 days after the start of voriconazole. Early and aggressive inspection including bronchoscopy should be performed for the diagnosis of Scedosporium infection in immunocompromised patients, even if CT scans and sputum culture show no evidence of infection.

Objectives One of the serious problems after lung transplantation is chronic lung allograft dysfunction (CLAD). Most CLAD patients pathologically characterized by obliterative bronchiolitis (OB). Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)-Ig is a combination protein of the Fc fragment of human IgG1 linked to the extracellular domain of CTLA4. The aim of the study was to examine the effect of CTLA4-Ig therapy on OB using a mouse intrapulmonary tracheal transplantation (IPTT) model. Methods IPTT was performed between BALB/c (donor) and C57BL/6 (recipient) mice. Abatacept, which is a commercially available form of CTLA4-Ig, was intraperitoneally injected in recipient mice immediately after surgery, on days 7, 14, and 21. The mice in the control group received human IgG. Results We performed semi-quantitative analysis of graft luminal obliteration at post-transplant day 28. We calculated the obliteration ratio of the lumen of the transplanted trachea in each case. The obliteration ratio was significantly lower in the CTLA4-Ig group than that in the control group (91.2 ± 2.1% vs. 47.8 ± 7.9%, p = 0.0008). Immunofluorescent staining revealed significantly decreased lymphoid neogenesis in the lung. Conclusions CTLA4-Ig therapy attenuated tracheal obliteration with fibrous tissue in the mouse IPTT model. The attenuation of fibrous obliteration was correlated with the inhibition of lymphoid neogenesis.

OBJECTIVES The objective of the present study was to examine the effect of venovenous (VV) extracorporeal membrane oxygenation (ECMO) use on the haemodynamics during single lung transplantation (SLT) and postoperative course. METHODS Forty-seven patients who underwent SLT for end-stage lung diseases in our lung transplant centre between January 2010 and December 2019 were included in this study. The recipients were divided into 3 groups according to the type of intraoperative ECMO. No type of ECMO was intra-operatively used in the patients of the no use of ECMO (NO ECMO) group. The patients in the venoarterial (VA) and VV ECMO groups were put on VA and VV ECMO during the surgery, respectively. The data were compared among the 3 groups. RESULTS There were 13 SLT cases in the NO ECMO group, 23 SLT cases in the VA ECMO group and 11 SLT cases in the VV ECMO group. Re-exploration for bleeding was performed in 3 (13.0%) recipients in the VA ECMO group. No recipients required re-exploration in the other groups. In the NO ECMO group, systolic pulmonary arterial pressure (PAP) was significantly elevated during the main pulmonary artery clamp on the SLT side and it was decreased in the VA ECMO group because of the bypass flow. Interestingly, systolic PAP was significantly decreased in the VV ECMO group as well. CONCLUSIONS VV ECMO decreases the PAP during SLT, which could be a choice for extracorporeal life support during lung transplant surgery for patients, even those with pulmonary hypertension.

Fluorouracil and leucovorin combined with oxaliplatin or irinotecan plus bevacizumab (Bmab) or cetuximab (Cmab) are now widely accepted treatment options as first-line or second-line chemotherapy for metastatic colorectal cancer (mCRC). Sequential chemotherapy with oral 5-FU backbone for mCRC without using central venous ports is beneficial for both patients and physicians. We designed the SOBIC trial to validate the effectiveness of the first- and second-line oral combination chemotherapy for mCRC. From May 2010 through March 2013, 52 patients were enrolled from 47 institutions in the Hyogo Colorectal Cancer Surgery Group. First-line chemotherapy was S-1 + oxaliplatin (SOX) plus Bmab, and second-line chemotherapy after first-line failure was irinotecan + S-1 (IRIS) + Cmab, IRIS + Bmab, or IRIS based on the KRAS status. The 50 finally included patients received first-line chemotherapy. Second-line therapy was administered to 20 patients (40%): 12 patients received IRIS + Cmab and 8 patients received IRIS + Bmab. The median follow-up period was 48.6 months (range 35–67 months). The median second progression-free survival was 24.2 months (95% confidence interval [CI] 17.7–35.2). The response rate after first- and second-line chemotherapy was 46.7% and 15%, respectively. The median overall survival was 35.2 months (95% CI: 27.8 to not reached). The main grade 3–4 adverse events were sensory neuropathy (18%) and fatigue (10%). There were no treatment-related deaths. Sequential S-1-based combination regimens including oxaliplatin, irinotecan, Bmab, and Cmab were beneficial for patients with mCRC.

The gastrointestinal tract is one of the locations that lung cancers cause metastasis. A 70-year-old male underwent right lower lobectomy while presenting fecal occult blood with a preoperative colonoscopy showing colon polyps as the cause. The pathological diagnosis was pleomorphic carcinoma of the lung, with stage pT3N0M0. Seven months after the lung surgery, the patient presented with sudden-onset abdominal pain and severe anemia. Computed tomography scanning revealed a large mass in the abdominal cavity, and subsequent intestinal endoscopy demonstrated jejunum tumors. Partial jejunum resection was successfully performed. The patient developed multiple peritoneal nodules suggesting metastatic tumors but well responded to an immune checkpoint inhibitor. It can be challenging to diagnose gastrointestinal metastasis in routine radiography; therefore, endoscopic examination, including the small intestine, might be an important option when a lung cancer patient with advanced clinical stage presents with abdominal symptoms, including fecal occult blood.

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. 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. 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). Invasion of the chest wall or parietal pleura is poor prognostic factors in T4 non-small cell lung cancer patients.

Background The median sternotomy approach in sleeve pneumonectomy enables diseased lung ventilation in selected cases, which may reduce the difficulty in achieving anastomosis under intubation of the left main bronchus. However, with median sternotomy, the ascending aorta requires repeated mobilization to expose the operative field for anastomosis, which can cause an aortogenic embolic stroke. Case presentation A 70-year-old Asian man presenting 6 months after developing hemoptysis was diagnosed with right upper lobe lung cancer (stage T4N0M0), invading the lower trachea and basal bronchus. Preoperative computed tomography revealed ascending aorta calcification. Right sleeve pneumonectomy was performed using median sternotomy with diseased lung ventilation. The ascending aorta was repeatedly mobilized to adequately expose the tracheobronchial bifurcation. Surgery was uneventful, but he did not recover complete consciousness even after termination of anesthesia. Mild paralysis of both upper extremities was observed. Head magnetic resonance imaging on postoperative day 1 revealed multiple small acute infarctions in the brain, possibly caused by mobilization of the aorta. He received anticoagulation therapy and rehabilitation and was discharged on postoperative day 30. Conclusion The median sternotomy approach in sleeve pneumonectomy enables diseased lung ventilation. However, the possibility of aortogenic embolic stroke should be considered when calcification of the ascending aorta is observed on preoperative computed tomography.

Background and Objectives To treat organ transplant patients with mycobacterial infection, physicians need to pay attention to interaction between drugs used against mycobacteria and immunosuppressants. The purpose of this report is to describe the clinical features of and treatment for mycobacterial infection in lung transplant (LTx) recipients. Methods To investigate the incidence, treatment, and outcome for mycobacterial infection, we retrospectively reviewed 100 LTx recipients in our program since 2000. Results Four recipients (4.0%) developed mycobacterial infection. Three recipients took tacrolimus, and 1 received cyclosporine with mycophenolate mofetil and a steroid for immunosuppression. Tuberculosis (TB) was isolated from 2 recipients, and non-tuberculous mycobacteriosis (NTM) was detected in the other 2. We treated the patients with levofloxacin + isoniazid + pyrazinamide + ethambutol (EB) for TB and clarithromycin (CLM) + EB for NTM to avoid interaction of calcineurin inhibitors (CNI: 8-10 ng/mL in trough level) with rifampicin (RFP). In treating the patients with NTM, we were able to maintain an adequate blood concentration of CNI by decreasing the dosage from one-half to one-quarter. All mycobacterial infections were controlled with treatment. In 1 patient with chronic obstructive pulmonary disease (COPD) infected with TB in the native lung, the forced expiratory volume in 1 second (FEV1) unexpectedly increased from 1890 mL before infection to 2320 mL possibly due to organization of the native lung. Conclusions We were able to manage the mycobacterial infections using drugs other than RFP without any cases of acute rejection under adequate immunosuppression. Organization of the native lung with TB infection unexpectedly resulted in improvement of FEV1 in a COPD patient.

The purpose of this study was to assess the usefulness of positron emission tomography/computed tomography (PET/CT) in the differential diagnosis of anterior mediastinal tumors. A total of 94 patients with anterior mediastinal masses or nodules (male, n = 41; female, n = 53; age, 17–84 years) were retrospectively evaluated. All patients were evaluated by PET/CT and the masses or nodules were histologically diagnosed in our institution. Anterior mediastinal masses and nodules were classified into two disease categories: Low (thymic hyperplasia, thymoma, mature teratoma, and MALT lymphoma) and High (thymic carcinoid, thymic cancer, diffuse large B-cell lymphoma, T-cell lymphoblastic lymphoma, Hodgkin’s lymphoma, and malignant germ cell tumors) groups. The sensitivity and specificity of maximum standardized uptake value (SUVmax) 7.5 for the detection of High group were 77% and 100%, respectively. The SUVmax distributions of the WHO histological thymoma types and Masaoka stage thymomas extensively overlapped. Masaoka stage III thymomas had significantly higher SUVmax than Masaoka stage I thymomas. Regarding the TNM classification, the SUVmax of T3 and T1b thymomas was higher than T1a thymoma. Although the SUVmax of each disease overlapped, PET/CT findings provided useful information for the differential diagnosis of anterior mediastinal masses.

Lung transplantation is accepted as an effective modality for patients with end-stage pulmonary lymphangioleiomyomatosis (LAM). Generally, bilateral lung transplantation is preferred to single lung transplantation (SLT) for LAM because of native lung-related complications, such as pneumothorax and chylothorax. It remains controversial whether SLT is a suitable surgical option for LAM. The objective of this study was to evaluate the morbidity, mortality and outcome after SLT for LAM in a lung transplant center in Japan. We reviewed the records of 29 patients who underwent SLT for LAM in our hospital between March, 2000 and November, 2017. The data collected included the pre-transplant demographics of recipients, surgical characteristics, complications, morbidity, mortality and survival after SLT for LAM. The most common complication after SLT for LAM was contralateral pneumothorax (n = 7; 24.1%). Six of these recipients were treated successfully with chest-tube placement and none required surgery for the pneumothorax. The second-most common complication was chylous pleural effusion (n = 6; 20.7%) and these recipients were all successfully treated by pleurodesis. The 5-year survival rate after SLT for LAM was 79.5%. LAM-related complications after SLT for this disease can be managed. SLT is a treatment option and may improve access to lung transplantation for patients with end-stage LAM.

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.

Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.

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.Our study objective was to evaluate the effect of SRT in BOS after LTx.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.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).SRT appeared to stabilize decline of FEV1 in patients with BOS possibly due to reducing the fluctuation of tacrolimus trough blood concentration.

Purpose This study assessed the incidence of malnutrition caused by preoperative chemoradiotherapy (CRT) in rectal cancer patients, which is seemingly underestimated; however, malnutrition affects treatment tolerability, postoperative complications, including anastomotic leakage (AL), and oncological outcomes. Methods Between January 2008 and December 2014, 54 consecutive patients with T3–4, N0–2, M0–1 resectable rectal cancer received CRT comprising 45 Gy radiotherapy and S-1 alone or with irinotecan for 5 weeks and then underwent curative surgery with diverting or permanent stomas 6–8 weeks after CRT. We assessed malnutrition after completion of CRT (5–6 weeks after CRT start date) and at surgery (11–14 weeks after CRT start date), defining weight loss as ≥5 % of pre-CRT weight; this definition differs from commonly used criteria for adverse events. We evaluated the incidence of malnutrition associated with CRT and influence of malnutrition on treatment tolerability, AL, and disease-free survival (DFS). We also assessed the influence of CRT on the rate of postoperative complications by comparing the study group with 61 patients who had undergone excision with diverting or permanent stomas alone. Results Malnutrition was observed in 51 % of patients after CRT and in 29 % at surgery. Malnutrition after CRT was associated with treatment tolerability, and malnutrition at surgery was significantly associated with AL, which significantly influenced DFS in stage 1–3 patients. Conclusion Malnutrition caused by CRT is common and is associated with treatment tolerability and AL. Nutritional assessment and support seem indispensable for the rectal cancer patients receiving CRT.

Purpose We developed an ex vivo lung CT (EVL-CT) technique that allows us to obtain detailed CT images and morphologically assess the retrieved lung from a donor for transplantation. After we recovered the lung graft from a brain-dead donor, we transported it to our hospital and CT images were obtained ex vivo before lung transplant surgery. The objective of this study was to investigate the correlation between the EVL-CT findings and post-transplant outcome in patients who underwent bilateral lung transplantation (BLT) or single lung transplantation (SLT). Methods We retrospectively reviewed the records of 70 patients with available EVL-CT data who underwent BLT (34 cases) or SLT (36 cases) in our hospital between October 2007 and September 2017. The recipients were divided into 2 groups (control group, infiltration group) according to the findings of EVL-CT of the lung graft in BLT and SLT, respectively. Recipients in the control group were transplanted lung grafts without any infiltrates (BLT control group, SLT control group). Recipients in the infiltration group received lung grafts with infiltrates (BLT infiltration group, SLT infiltration group). Results The recipients in the BLT infiltration group showed significantly slower recovery from primary graft dysfunction and a longer mechanical ventilation period and ICU stay period than those in the BLT control group. The mechanical ventilation period was significantly longer in the recipients in the SLT infiltration group than those in the SLT control group. Conclusion EVL-CT may predict the outcome of the early phase after lung transplantation.

Background. Acute kidney injury (AKI) is a common complication after lung transplant (LTx), and continuous renal replacement therapy (CRRT) is increasingly of use to critically ill patients who have developed AKI. However, the optimal timing or threshold of kidney impairment for which to commence CRRT after LTx has been uncertain. There has also been limited information on the impact of CRRT among LTx recipients (LTRs) introduced in the early posttransplant period on survival, graft function, and renal function. We aimed to review LTRs who developed AKI requiring CRRT postoperatively and followed their long-term outcomes at Tohoku University Hospital (TUH). Methods. Medical records of consecutive patients who underwent LTx at TUH between 2000 and 2018 were reviewed, with follow-up to 2019 inclusive. Results. Although mortality in those who required CRRT (n = 21) was increased versus those who did not require CRRT (n = 85)(P = 0.024), conditional survival beyond 3-month posttransplant was not affected (P = 0.131). Additionally, the cumulative incidence of chronic lung allograft rejection (P = 0.160) and the development of chronic kidney disease (P = 0.757) were not significant between groups. Conclusions. The initiation of CRRT posttransplant may be a useful strategy to preserve cardiac and optimize volume management among critically ill patients.

In the original publication, Fig. 3 has been incorrectly published. The correct version of Fig. 3 is given in this Correction.

Here, we report the case of a 40-year-old male with a giant intra-abdominal desmoid tumor (DT). He was followed up for familial adenomatous polyposis since age 17 years because of positive family history. Three years before admission, he was diagnosed with an inoperable intra-abdominal DT. He underwent surgery for peritonitis and received hormone and cyclooxygenase-2-inhibitor therapies. Eventually, the DT enlarged and perforated the abdominal wall. He presented with malnutrition, >5 L/week of effusion, anemia due to bleeding, pain, and a foul odor, all of which were attributed to the malignant wound. He was referred to our department for chemotherapy with dacarbazine plus doxorubicin. Chemotherapy after admission proved to be intolerable and ineffective. To relieve the patient’s condition, we applied Mohs’ paste on the tumor surface. Thereafter, the volume of effusion decreased to

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.

We report a case of bilateral lung transplantation (BLT) after preservation of the donor graft for 16 h 5 min with EP-TU, an extracellular phosphate-buffered lung preservation solution. The recipient was a 26-year-old woman with idiopathic pulmonary arterial hypertension and the graft ischemic time was prolonged significantly because of the time required to induce peripheral veno-arterial extracorporeal membrane oxygenation (V-A ECMO) under local anesthesia, and address the severe intrathoracic and pericardial adhesions from past surgery for partial anomalous pulmonary venous return, with concurrent annular plication of the tricuspid valve. After the operation, ECMO and continuous hemodiafiltration were started preemptively to protect the grafts against excessive edema. Postoperative chest X-ray showed diffuse bilateral infiltrates, which improved within a few days and she was weaned off ECMO on day 9. Successful BLT after a graft ischemic time of over 16 h has rarely been described in clinical lung transplantation.

Purpose CTLA4-Ig has been used as a treatment for rheumatoid arthritis in clinical practice. CTLA4-Ig was reported to induce lymphocyte-activation gene 3 positive regulatory T cells (LAG3+ Tregs), which produce high amounts of IL-10. This effect on LAG3+Tregs is thought to be one of the mechanisms of the therapeutic effect of CTLA4-Ig in rheumatoid arthritis patients. Recently, CTLA4-Ig was reported to improve long-term outcomes in kidney transplant recipients. We hypothesized that CTLA4-Ig can attenuate chronic lung allograft dysfunction (CLAD) after lung transplantation. The objective of this study was to investigate the effects of CTLA4-Ig therapy in a mouse intrapulmonary tracheal transplantation (IPTT) model, which is an animal model of CLAD. Methods C57BL/6 (B6) mice received IPTT from major-mismatched BALB/c donors. B6 mice were randomly divided into 2 groups. In the CTLA4-Ig group (n = 13) , recipient mice were intraperitoneally injected with 500 µg of CTLA4-Ig immediately after IPTT and on day 7, 14 and 21. In the control group, recipients (n = 11) were injected with 500 µg of human IgG in the same manner. After recipient animals were sacrificed on day 28, Masson's trichrome staining of the extracted left lung and semiquantitative analysis of the graft lumenal obliteration were conducted. Real-time PCR of the lung was performed (another set of groups were made for the analysis; CTLA4-Ig n = 9, control group n = 7). Results The lumenal obliteration ratio in the tracheal allografts was significantly reduced in the CTLA-Ig group (63.0 ± 7.51% vs. 90.1 ± 2.22%, p = 0.004) (Figure A, B). Real-time PCR of the lung revealed that the gene expression ratio of LAG3 to CD4 expression (LAG3/CD4) ratio was significantly upregulated in the CTLA4-Ig group (2.81 ± 0.71 vs. 0.98 ± 0.12, p = 0.041) (Figure C). Conclusion CTLA4-Ig attenuated the fibrous airway obliteration in the mouse IPTT model. CTLA4-Ig may promote LAG3+Treg-mediated anti-inflammatory effects.

In solitary fibrous tumors (SFTs) of the pleura, malignant SFTs are uncommon. Although SFTs are known to cause paraneoplastic syndromes through the production of insulin-like growth factor, to the best of our knowledge, the production of beta-human chorionic gonadotropin (β-hCG) has been reported only in 1 case involving a patient with a benign SFT. We herein report the first case of the elevation of β-hCG serum levels associated with a malignant SFT in which the β-hCG serum level became a useful indicator of recurrence after the complete resection of the primary mediastinal lesion.

Primary pulmonary choriocarcinoma is a very rare tumor and eventually diagnosed by pulmonary resection. A poor prognosis has been reported for this disease, but appropriate treatment has not been established. Here, we report the successful surgical treatment for a primary pulmonary choriocarcinoma. A 70-year-old male presented with cough and a 3.8-cm solid tumor was detected in the right upper lobe of the lung on CT scan. Results of an open lung biopsy indicated carcinoma with indeterminate histological subtype. Right upper lobectomy was performed and the permanent pathological diagnosis was choriocarcinoma. Right after surgery, systemic and genital screening was performed by urologist, but no abnormal findings were observed. Elevation of serum β-hCG was confirmed at the same time and the value dropped within normal range in 2 months. According to diagnosis criteria, we reached final diagnosis of primary pulmonary choriocarcinoma. The patient has been alive with no recurrence for 2 years after surgery.

The aim of this study was to clarify the clinical aspects, histopathological features and prognosis of patients with rectal carcinoids, focusing on properties associated with metastasis, in order to gain insights into appropriate management. A total of 20 patients (15 males, 5 females; mean age, 54.9 years; range, 23-71) who underwent surgery for rectal carcinoid tumors at the Department of Colorectal Surgery, Hyogo College of Medicine, between May 2000 and January 2011 were analyzed. Ki-67 immunostaining was performed in 13 cases with available tumor tissue specimens. Of the 20 patients, a radical operation including rectal resection with a lymphadenectomy was performed in 16. The mean tumor size was 11.9 mm (3-25 mm) and lymph node metastasis was confirmed in 9 cases, including 3 with lesions no greater than 7 mm in diameter. Overall, 16 (80%) of the tumors were localized in the submucosal layer and 4 (20%) involved the proper muscle layer. Ki-67 labeling index and lymphovascular invasion were shown to be associated with lymph node and/or distant metastasis by multiple logistic regression analysis, but were not statistically significant in ANOVA findings. Lymph node metastasis from rectal carcinoids, even those smaller than 10 mm in diameter, was not a rare event. More attention should be given to decision-making, including the possibility of endoscopic resection for the treatment of rectal carcinoid tumors regardless of size.

A 62-year-old man was pointed out the superior sulcus tumor of the left lung invading to the subclavian artery and the vertebral artery. Bronchoscopic brushing cytology of the tumor showed Class V large cell carcinoma. The patient was diagnosed as clinical stage IIIA(cT4N0M0). After concurrent chemoradiotherapy, we performed left-upper lobectomy and reconstructions of left subclavian and vertebral arteries through modified transmanubrial approach. Surgeons of three different departments took part in the operation. Cooperative works were the key for the complete resection of such an advanced superior sulcus tumor.

Objectives The purpose of the present study was to retrospectively compare the outcomes of video-assisted thoracic surgery in awake and anesthetized patients in the treatment of secondary spontaneous pneumothorax. Methods A total of 57 consecutive patients who underwent video-assisted thoracic surgery for secondary spontaneous pneumothorax was retrospectively analyzed. Of these patients, 15 underwent surgery under epidural and/or local anesthesia (ELA) and 42 under general anesthesia. Using propensity score matching, we identified comparable patient groups: the ELA group and general anesthesia group (n = 8 each). We compared the duration of operating room stay, operating time, postoperative hematologic data on postoperative day 1, postoperative complications, duration of hospital stay, and the incidence of hospital death between the ELA and general anesthesia groups. Results After propensity score matching, the duration of operating room stay was significantly shorter in the ELA group ( P = .006). The incidence of postoperative respiratory complications, including pneumonia and acute respiratory distress syndrome, was lower in the ELA group ( P = .02). The duration of postoperative hospital stay and the incidence of hospital death were not different between the 2 groups. Conclusions The ELA group had a lower incidence of postoperative respiratory complications. Awake video-assisted thoracic surgery can be performed with an acceptable overall morbidity for patients with secondary spontaneous pneumothorax.

We evaluated the effect of an extracellular phosphate-buffered lung preservation solution (EP-TU solution) on acute postoperative graft function and recipient survival in a Japanese series of cadaveric lung transplantation.The subjects were ten patients who received lung grafts preserved with EP-TU solution at three of four designated lung transplant centers between 2000 and 2005. Three of the patients underwent single lung transplantation and seven underwent bilateral lung transplantation. Postoperative graft function was evaluated by primary graft dysfunction (PGD) grade (0-3), arterial oxygen tension/inspired oxygen fraction (PaO(2)/FiO(2)) ratio, and the previously reported chest roentgenogram score (CRS, 0-4) during the first 48 h after intensive care unit admission. Survival rates were also calculated.The average graft ischemic times for the first and second grafts were 431 and 571 min, respectively. The average PGD grade ranged from 0.5 to 1.0 and the average PaO(2)/FiO(2) ratio ranged from 350 to 400 Torr during the 48 h. The average CRS was always under 1.0. Survival rates at 30 days and 5 years were 90 and 80%, respectively.EP-TU solution promoted excellent postoperative lung graft function and enhanced recipient survival rates, despite a long average preservation time.

We herein present five cases of bilateral intractable secondary spontaneous pneumothorax associated with chronic severe lung diseases that were successfully treated with a modified form of a previously reported surgical procedure, the "total pleural covering technique," under video-assisted thoracic surgery. We performed the total pleural covering technique modified with a preceding coverage of air-leak points with polyglycolic acid sheets. In this series, the median length of surgery was 106 min (range: 67-220 min) on the unilateral side (10 sides). No significant surgical complications were observed, but one patient died on day 23 after the operation, due to respiratory insufficiency on the basis of the underlying lung disease. The remaining four patients have been followed up regularly (mean follow-up time: 23 months; range: 1-54 months) and there has been no recurrences of pneumothorax. We believe that the total pleural covering technique is a useful method; however, special attention should be paid to the underlying disease in order to identify patients who would be most likely to benefit from the procedure.

A 14-year-old female patient underwent right single living-donor lobar lung transplantation for bronchiolitis obliterans after bone marrow transplantation. The patient experienced a complication with severe hypoxemia requiring venovenous extracorporeal membrane oxygenation, which appeared to result from significant ventilation-perfusion mismatch caused by preferential ventilation of the transplanted lobe and relatively preserved perfusion to the native lung. On day 2, we performed left pulmonary artery banding, which significantly improved oxygenation leading to weaning from extracorporeal membrane oxygenation. Our experience indicates that contralateral pulmonary artery banding may be a feasible option to rescue patients from hypoxemia resulting from ventilation-perfusion mismatch after single living-donor lobar lung transplantation.

Background The ability to express genes with potential immunoregulatory capacity could reduce allograft rejection (AR). This study examined the effect of ex vivo lipid-mediated transbronchial human interleukin-10 (hIL-10) gene transfer on AR and the intragraft cytokine profile in a rat model of lung transplantation. Methods Left single lung transplants were performed between a highly histoincompatible combination of inbred rats. The donor left lung was extracted and intrabronchially instilled with a plasmid encoding hIL-10 (IL-10 group) or Escherichia coli β-galactosidase (control group), mixed with a cationic lipid. At 3 and 6 days after transplantation, the degree of AR was graded histologically (stage 1–4) and several pathologic categories of inflammation were scored on a scale of 0 to 4 according to the percentage of involvement. Intragraft cytokine profile was examined by real-time reverse transcription polymerase chain reaction. Results The stage of AR (3.1 ± 0.4 vs 3.8 ± 0.4) and the pathologic scores for edema (2.3 ± 0.8 vs 3.2 ± 0.4), intraalveolar hemorrhage (0.3 ± 0.5 vs 2.2 ± 0.8), and necrosis (0.3 ± 0.5 vs 1.2 ± 0.4) in the IL-10 group were significantly decreased compared with the control group at Day 6. IL-2 and tumor necrosis factor-α messenger RNA expression levels on Day 3 were significantly decreased in the IL-10 group. Conclusions Ex vivo lipid-mediated transbronchial hIL-10 gene transfer attenuated acute inflammation associated with AR, which was related to decreased levels of proinflammatory cytokine gene expression in a rat model of lung transplantation.

症例は19歳，女性．う歯に起因したLemierre症候群による続発性気胸の診断で当科紹介，転院した．胸腔ドレナージで気漏が遷延したため，肺部分切除，および気漏閉鎖術を行った．術後に気漏の再発を認め，広背筋弁による筋肉充填術を行った．再手術後も気漏の再発を認め，フィブリン糊胸腔内大量注入療法を繰り返しつつ，栄養状態の改善を行ったところ気漏が消失した．Lemierre症候群に続発する気胸は難治性であり，今回，強力な全身的感染制御と栄養状態の改善とともに，手術，フィブリン糊胸腔内大量注入療法による集学的治療が有効であった．

クローン病(以下CD）における痔瘻，肛門周囲膿瘍の合併頻度は高く，多発性，難治性であることを特徴とする．治療に際しては，肛門機能温存，癌合併などの問題に配慮が必要である．今回，難治性痔瘻，肛門周囲膿瘍に対し，手術を行ったCD108症例につき検討した．括約筋温存，再発防止を目的に，当科ではsetonドレナージを基本術式としている．軽快例は85.2%であったが，再手術を必要とした症例は39.8%，累積再手術率は5年で32.4%であった．Seton併用の有無に関する再手術率は併用群31.3%，非併用群68.0%と有意差を認めたが，最終的に人工肛門造設となった症例は各々16.9%，16.0%で有意差はなかった．直腸腟瘻を有する症例は11例あったが，全例軽快せず，人工肛門造設5例，直腸切断術2例と難治性であった．Seton法は根治性には乏しいが再発予防には効果があり，CDの難治性痔瘻，肛門周囲膿瘍に対する手術療法では選択するべきであると考えられた．

【目的】難治性気胸の術後合併症リスク評価．【対象と方法】高齢者難治性気胸手術症例43例に対し，術前背景因子，術前臓器機能因子，術前評価可能な麻酔手術侵襲等について比較検討し，単変量解析によるリスク評価を行った．続いて多変量解析を行い，高齢気胸術後合併症リスク評価を試みた．【結果】男性41例女性2例で，術後合併症は10例（23.3％）で認められた．諸因子別網羅的解析では，全25項目中血清TP，Alb，chE，Na＋低値群およびPS，酸素投与群，麻酔スコア値で有意であった．すべての因子による多変量解析ではPS低値群にて有意に合併症が発生した（odds比：73.7，P＝0.003）．【結語】高齢者難治性気胸ではperformance status不良，低栄養状態，低Na群および酸素吸入群は全身麻酔手術ハイリスク群である．

症例は53歳女性．約10年の潰瘍性大腸炎(UC）加療中，サーベイランス大腸内視鏡検査でdysplasia associated lesion or mass(DALM）を指摘．結腸全摘，直腸粘膜切除，J型回腸嚢肛門吻合術(IPAA）を施行．大腸に扁平上皮癌(粘膜切除部，直腸），粘液癌(下行結腸），高分化型腺癌(上行結腸，横行結腸）と多彩な病理形態のcancerを認めた．いずれもpM, pN0, stage Iで，良好に経過している．近年，サーベイランス大腸内視鏡の有用性が広く認識され，DALMが手術適応のUC症例は増加している．肛門温存術式が標準術式となっているが，IPAAまたは回腸嚢肛門管吻合(IACA）の選択には一定の見解が得られていない．肛門管粘膜の発癌に関しては低頻度であり，問題ないとする報告があるが，粘膜切除部に癌を認める症例も少なからず存在し,直腸粘膜切除が必要となる症例が存在するものと思われた．

目的：潰瘍性大腸炎(以下UC）患者において，回腸嚢肛門吻合術(以下IPAA）を行った症例で，粘膜切除部に癌を合併した症例の臨床的特徴を検討し，粘膜切除を行うことが望ましい患者群を明らかにすること．対象と方法：2003年1月から2006年12月までにIPAAを行った全症例319例の肛門管粘膜切除部の病理検査を行った．直腸粘膜切除部断端(歯状線部）から2.5cmまでを粘膜切除部と定義した．結果：319例中4例(1.3%）の粘膜切除部に癌の合併を認めた．手術適応は1例が高分化型腺癌で，残りの3例はhigh grade dysplasia(以下HGD）であった．切除標本の病理検査では4例ともに癌病変の多発が認められた．組織型は2例が高分化型腺癌で，残りの2例が扁平上皮癌であった．深達度は1例にsm浸潤が認められたが，残りの3例は粘膜内癌であった．結語：大腸にHGDを認めるUC症例は多発病変が多く, 粘膜切除部にも癌が合併する可能性があり, 粘膜切除をともなうIPAAの適応であると思われた．

2006年12月までに当科で手術を行った潰瘍性大腸炎(以下UC）症例902例のうち，穿孔で手術適応となった28症例につき，その臨床的特徴について検討した．炎症性腸疾患(以下IBD）における穿孔はクローン病，ベーチェット病に多いとされ，UCでは比較的少ないとされている．しかしUC穿孔症例では活動期，ステロイド大量投与症例が多く，surgical site infection(SSI）を初めとする術後合併症は高頻度に見られ，管理に苦渋した．さらに疾患の性質上，若年者が多く，QOLを考慮して可能な限り肛門温存に努めるべきであり，当科症例28例中24例(85.7%）に肛門温存手術が可能であった．

2005年7月までに当科で手術を行った潰瘍性大腸炎 (以下UC) 症例755例のうち, 60歳以上の症例を高齢者と定義し, その臨床的特徴について検討した. 高齢者のUC手術症例は増加傾向にあり, 最近5年の症例では11.1%の症例が60歳以上であった. 手術術式は患者の術前の状態により多岐にわたっていた. 高齢者手術症例の予後を待機手術と緊急手術で比較検討すると, 緊急手術では15例中7人 (46.7%) が術後死亡しており, 予後は有意に不良であった. 死亡原因としては, MRSAや真菌感染に由来する呼吸器合併症や敗血症が多く見られた. 高齢者の重症UC症例は予備能力が小さく, 若年者に比べて予後は極めて不良であるため, このような患者の治療には, 消化器内科医と外科医が緊密な連絡を取りながら, 手術時期が遅れないようにすることが重要であることが示唆された.

家族性大腸腺種症 (FAP) や潰瘍性大腸炎 (UC) に対する1期的大腸全摘 (RPC), 回腸嚢肛門吻合術 (IAA) を腹腔鏡を用いないビキニラインアプローチ法で施行した女性患者16症例 (FAP4例, UC12例) を対象としその有用性を検討した. 平均年齢は27.1歳で平均手術時間は236.7分, 平均出血量196.3ml であった. 平均術後在院日数は24.5日で術中および術後に重篤な合併症は認めなかった. 同時期に施行された従来の正中切開法18例と比較すると手術時間は従来法 (208.9分) に比し有意に長かったが出血量, 術後在院日数, 合併症の頻度に有意差はなく患者の満足度も高かった. 本術式では鏡視下手術設備や器具は必要とせず安全に合併症なく施行できた. 美容的にも優れ, 特に若年女性には有用と思われた.

Mesenchymal stem cells (MSCs) suppress inflammation and immune responses. We conducted this study to find out if MSCs attenuate ischemia–reperfusion injury in a mouse model of lung transplantation. C57BL/6J mouse lungs perfused with low-potassium dextran glucose solution were preserved at 4 °C for 18 h. Human MSCs were slowly injected into the left pulmonary artery of the lung grafts, and orthotopic left lung transplantation was then performed. The lung isografts were reperfused for 6 h, and bronchoalveolar lavage fluid (BALF) from the left lung graft was collected. We measured the protein concentration, cell count, and proinflammatory cytokine concentrations in the BALF. The protein concentration and cell count in the BALF were significantly lower in the MSC-administered grafts than in the PBS-administered controls. Concentrations of proinflammatory cytokines, including IL-1β, IL-17A, and TNF-α, in BALF tended to be lower in the MSC-administered grafts than in the controls, but the difference was not significant. The pre-transplant administration of MSCs via the pulmonary artery of the lung graft attenuated ischemia–reperfusion injury after prolonged cold ischemia in this mouse model of lung transplantation.

Awake video-assisted thoracic surgery (VATS) is a therapeutic option for patients with intractable secondary spontaneous pneumothorax (SSP) complicated by impaired pulmonary function. The preoperative identification of air leak points is one of the keys to the success of this procedure. We describe how we performed saline-filled computed tomography (CT) thoracography to detect pleural fistulae in three patients with intractable SSP. Saline-filled CT thoracography showed bubble signs in two patients and an air–water level in bulla in one patient. The preoperative identification of air leak points resulted in successful awake VATS for all three patients. Our experience demonstrates that saline-filled CT thoracography is a useful diagnostic tool for SSP, especially when used in preparation for awake VATS when minimally invasive procedures are desirable.

We evaluated the incidence of dysplasia in the mucosectomy area using resected specimens to determine preoperative risk factors for the occurrence of dysplasia in this area.We prospectively studied a consecutive series of 137 patients, each of whom underwent a restorative proctocolectomy with a mucosectomy and hand-sewn ileal J-pouch anal anastomosis between January 2003 and December 2004. Sections from the anal transitional zone mucosa were taken from the dentate line to 2.5 cm above the resected line and stained with hematoxylin and eosin then characterized as indefinite for dysplasia, low-grade dysplasia, and high-grade dysplasia based on the criteria of an international working group for rectal mucosal atypia.Dysplasia of the mucosectomy area was present in six (4.4%) of the patients, including one with low-grade and five with high-grade dysplasia. A multivariate analysis showed relations between age at time of surgery (or=40 years) and duration of disease (or=10 years) with a risk for development of mucosectomy area dysplasia.The incidence of dysplasia of the mucosectomy area was 4.4%, and preoperative risk factors were shown to be duration of disease and age at time of surgery.

Background: The prevalence and significance of joint symptoms appearing in patients with ulcerative colitis (UC) following a colectomy are unclear. Aim: We investigated the relationship between joint symptoms during steroid tapering following an ileal pouch-anal anastomosis (IPAA) and the cumulative risk for developing pouchitis. Patients and Methods: The medical records of 571 patients who underwent an IPAA with a mucosectomy were retrospectively reviewed to evaluate their joint symptoms. A diagnosis of pouchitis was obtained using the Pouchitis Disease Activity Index (PDAI) and the cumulative risk of pouchitis was estimated using a Kaplan-Meier life table analysis. Results: Joint symptoms during steroid tapering were reported by 126 (22.0%) of the UC patients and each of those had involvement of the small joints of the hand. The main symptoms were pain and stiffness, especially in the morning. The cumulative risk for developing pouchitis after 10 years was found to be 20% in patients who experienced joint symptoms during steroid tapering and 10% in those without those symptoms (p = 0.001). Conclusion: The presence of joint symptoms during steroid tapering is a significant risk factor for the development of pouchitis in patients who have undergone an IPAA for UC.

Purpose. To evaluate the effectiveness of Seprafilm in preventing abdominal adhesions after radical resection of rectal carcinoma, and to observe whether Seprafilm had any adverse effects in patients treated with radiotherapy and chemotherapy. Methods. A total of 62 patients participated in this prospective randomized clinical study, which was conducted to compare the outcomes of patients operated on with Seprafilm (SEPRA+) with those operated on without Seprafilm (SEPRA-). All patients received preoperative radiotherapy, followed by a two-stage operation, and 5-fluorouracil (5-FU)-based systemic chemotherapy. The primary endpoint of severity and extent of adhesions were evaluated at the time of ileostomy closure. The secondary endpoint included the recurrence of tumors, late complications, and outcome. Results. Seprafilm significantly reduced the adhesions in both the midline incision area and peristomal area. This in turn reduced the operation time, blood loss, and extent of the incision at ileostomy closure. Seprafilm was not associated with any postoperative complications or chemoradiation-related toxicity, nor did it affect recurrence or survival rates. Conclusion. Seprafilm effectively reduced abdominal adhesions in chemoradiated patients, and had no adverse effects on the oncologic results of fully introduced adjuvant therapy. Thus, Seprafilm is a safe and effective tool for use in rectal carcinoma surgery.

A 31-year old female patient in the ninth week of pregnancy complained of chest pain and dyspnoea. The patient had experienced an episode of spontaneous pneumothorax on the left side at the age of 20 and had undergone chest tube drainage. Her medical history was unremarkable and she had no history of smoking. She had no family history of pulmonary disease. Thoracic radiography showed a pneumothorax on the right side. The patient underwent chest tube drainage in the thoracic space. When surgical intervention for continuous air leakage was unavoidable, we selected video-assisted thoracic surgery under local and epidural anaesthesia in consideration of her general condition. We conclude that awake surgical intervention is applicable in selected patients with pneumothorax in pregnancy and is particularly useful in those in whom general anaesthesia is best avoided.