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Purposes: Robot-assisted thoracoscopic (RATS) segmentectomy is becoming increasingly common because of the expanded indications for segmentectomy and the widespread adoption of robotic surgery. The precise division of the intersegmental plane is necessary to ensure oncologic margins from the tumor and to preserve the lung function. In this study, we present a strategy for accurately dividing the intersegmental plane using a robotic stapler and review the surgical outcomes., Methods: RATS portal segmentectomy was performed using the Da Vinci Xi system and the intersegmental plane was dissected using a robotic stapler. We evaluated the perioperative outcomes in 92 patients who underwent RATS portal segmentectomy between May 2020 and January 2023. These results were compared with those of 82 patients who underwent complete video-assisted thoracoscopic surgery (CVATS) during the same period., Results: The operative and console times were 162 and 97 min, respectively. No intraoperative complications occurred, and postoperative complications were observed in four cases (4.3%). The operative time, blood loss, postoperative complications, and maximum incision size were significantly lower in the RATS group than in the CVATS group. However, RATS requires a significantly higher number of staplers than CVATS., Conclusions: The division of the intersegmental plane using a robotic stapler in RATS portal segmentectomy was, therefore, found to be safe and effective., (© 2024. The Author(s).)

Purpose: Radiation pneumonitis (RP) is an obstacle for patients after surgery following induction chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). We performed a comparative analysis of the association between clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and prognosis, in LA-NSCLC patients with or without RP during induction chemoradiotherapy followed by surgery., Methods: The subjects of this analysis were 168 patients undergoing trimodality therapy for LA-NSCLC between January, 1999 and May, 2019. Patients were divided into two groups: the RP group (n = 41) and the non-RP group (n = 127). We compared the clinicopathological factors including the NLR between the groups and analyzed the association between the NLR and prognosis., Results: The RP group had more patients with tumors located in the lower lobe, more bilobar resections, shorter operative times, no implementation of postoperative adjuvant chemotherapy, and a higher postoperative NLR than the non-RP group. There were no significant differences in serious postoperative complications and the prognosis. Patients with a low postoperative NLR had a significantly better prognosis in the non-RP group, and a trend toward a better prognosis even in the RP group., Conclusion: Postoperative NLR may be a useful prognostic factor, even for patients who suffer RP after trimodality therapy for LA-NSCLC., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: Bronchopleural fistula (BPF) is a serious complication of lung resection. To avoid BPF, the bronchial stump/anastomotic site is often covered with a flap of surrounding tissue. One risk factor for BPF is radical lung resection after induction chemoradiotherapy for lung cancer. We retrospectively reviewed our database to elucidate the characteristics of tissue flaps that prevent BPF., Methods: This retrospective study included 152 patients treated between 1999 and 2019. We examined the clinicopathological characteristics, including the type and thickness of the tissue flap used to cover the bronchial stump/anastomotic site, and postoperative complications, including BPF., Results: BPF occurred in 5 patients (3.3%). All 5 patients had complications that could have affected delayed wound healing, such as pneumonia. The covering tissue flap thickness was significantly greater in patients without BPF than in those who developed BPF (p = 0.0290). Additionally, the tissue flap thickness was significantly greater than in those with BPF (p = 0.0077), even in high-risk patients who developed pneumonia or radiation pneumonitis on the operative side within 6 months postoperatively., Conclusion: Perioperative management is crucial to avoid complications affecting the healing of the bronchial stump/anastomotic site, and the covering tissue flap thickness may be an important factor in avoiding or minimizing BPF., (© 2024. The Author(s).)

Purpose: Chronic lung allograft dysfunction (CLAD) is a known long-term fatal disorder after lung transplantation. In this study, we evaluated the CLAD classification of the International Society for Heart and Lung Transplantation (ISHLT) for living-donor lobar lung transplantation (LDLLT)., Methods: We conducted a single-center retrospective review of data from 73 patients who underwent bilateral LDLLT between 1998 and 2019. Factors related to opacity on computed tomography (CT) and restriction on pulmonary function tests (PFTs) were also analyzed., Results: Overall, 26 (36%) patients were diagnosed with CLAD, including restrictive allograft syndrome (RAS), n = 10 (38.5%); bronchiolitis obliterans syndrome (BOS), n = 8 (30.8%); mixed, n = 1 (3.8%); undefined, n = 2 (7.7%); and unclassified, n = 5 (19.2%). The 5-year survival rate after the CLAD onset was 60.7%. The survival of patients with BOS was significantly better than that of patients with RAS (p = 0.012). In particular, patients with restriction on PFT had a significantly worse survival than those without restriction (p = 0.001)., Conclusions: CLAD after bilateral LDLLT does not have a major impact on the recipient survival, especially in patients with BOS. Restriction on PFT may predict a particularly poor prognosis in patients with CLAD after bilateral LDLLT., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Cancer-associated fibroblasts (CAFs) are important components in the tumor microenvironment, and we sought to identify effective therapeutic targets in CAFs for non-small cell lung cancer (NSCLC). In this study, we established fibroblast cell lines from the cancerous and non-cancerous parts of surgical lung specimens from patients with NSCLC and evaluated the differences in behaviors towards NSCLC cells. RNA sequencing analysis was performed to investigate the differentially expressed genes between normal fibroblasts (NFs) and CAFs, and we identified that the expression of periostin (POSTN), which is known to be overexpressed in various solid tumors and promote cancer progression, was significantly higher in CAFs than in NFs. POSTN increased cell proliferation via NSCLC cells' ERK pathway activation and induced epithelial-mesenchymal transition (EMT), which improved migration in vitro. In addition, POSTN knockdown in CAFs suppressed these effects, and in vivo experiments demonstrated that the POSTN knockdown improved the sensitivity of EGFR-mutant NSCLC cells for osimertinib treatment. Collectively, our results showed that CAF-derived POSTN is involved in tumor growth, migration, EMT induction, and drug resistance in NSCLC. Targeting CAF-secreted POSTN could be a potential therapeutic strategy for NSCLC. KEY MESSAGES: • POSTN is significantly upregulated in CAFs compared to normal fibroblasts in NCSLC. • POSTN increases cell proliferation via activation of the NSCLC cells' ERK pathway. • POSTN induces EMT in NSCLC cells and improves the migration ability. • POSTN knockdown improves the sensitivity for osimertinib in EGFR-mutant NSCLC cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Although the performance lung transplantation (LTx) in the elderly (≥ 60 years) has increased globally, the situation in Japan remains quite different, because the age limit at registration for cadaveric transplantation is 60 years. We investigated the long-term outcomes of LTx in the elderly in Japan., Methods: This was a single-center retrospective study. We divided the patients into two groups according to age: the younger group (< 60 years; Y group; n = 194) and the elderly group (≥ 60 years; E group; n = 10). We performed three-to-one propensity score matching to compare the long-term survival between the E and Y groups., Results: In the E group, the survival rate was significantly worse (p = 0.003), and single-LTx was more frequent (p = 0.036). There was a significant difference in the indications for LTx between the two groups (p < 0.001). The 5-year survival rate after single-LTx in the E group was significantly lower than that in the Y group (p = 0.006). After propensity score matching, the 5-year survival rates of the two groups were comparable (p = 0.55). However, the 5-year survival rate after single-LTx in the E group was significantly lower than that in the Y group (p = 0.007)., Conclusion: Elderly patients showed acceptable long-term survival after LTx., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Objectives: We herein review the outcomes of paediatric lung transplantation (LTx) and analyse subgroups divided by age., Methods: We retrospectively reviewed 43 consecutive paediatric LTx recipients (< 18 years old: cadaveric LTx [n = 9], living-donor lobar LTx [n = 34]). We also analysed subgroups of patients 1-6 years old (n = 10) and 7-17 years old (n = 33)., Results: The 1-, 5- and 10-year overall survival (OS) rates in paediatric recipients were 93%, 82% and 67%, respectively. The 1-, 5- and 10-year graft dysfunction (GD)-free survival rates in paediatric recipients were 85%, 59% and 31%, respectively. The 1- and 5-year OS in the 1- to 6-year-old vs. 7- to 17-year-old groups were 70% vs. 100% and 48% vs. 93%, respectively (p < 0.0001). The 1- and 5-year GD-free survival rates in the 1- to 6-year-old vs. 7- to 17-year-old groups were 60% vs. 93% and 24% vs. 69%, respectively (p = 0.024). The 1- to 6-year-old group showed higher rates of non-standard LTx (p = 0.0001), interstitial pneumonia (p = 0.004) and ventilator dependency (p = 0.007) than the 7- to 17-year-old group., Conclusion: Paediatric recipients under 7 years old seemed to have a higher risk of mortality and GD than those 7 years old and older., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: Post-transplant lymphoproliferative disorder (PTLD) is a major complication of lung transplantation (LTx). However, few studies on PTLD in Asian populations have been reported. We explored the characteristics of Japanese PTLD cases after LTx., Methods: We retrospectively reviewed 195 cases of LTx at our institute. We summarized the clinical experiences of 7 PTLD cases and analyzed the patient characteristics and survival outcomes of patients with (n = 7) and without (n = 188) PTLD., Results: All PTLD patients were taking corticosteroids preoperatively (p = 0.0030), and the duration of preoperative corticosteroid therapy was significantly longer in the PTLD group (p = 0.0064) than in the non-PTLD group. The overall survival after LTx was significantly worse in the PTLD group (p = 0.027) than in the non-PLTD group. Among the three patients who died within 1 year after the PTLD onset, two died of opportunistic infections without residual PTLD lesions. Chronic lung allograft dysfunction (CLAD) or bronchiolitis obliterans at an autopsy were diagnosed after PTLD treatment in four cases., Conclusions: Long-term preoperative corticosteroid therapy may be a risk factor for PTLD after LTx. Opportunistic infections are lethal complications of PTLD, regardless of the effectiveness of PTLD treatment. CLAD occurs at a high rate after PTLD treatment, and close monitoring is required., (© 2021. Springer Nature Singapore Pte Ltd.)

Purpose: Decreased irisin levels may be associated with the development of emphysema. Similarly, emphysematous changes may develop in patients with chronic lung allograft dysfunction (CLAD) after living-donor lobar lung transplantation (LDLLT). We investigated the severity of emphysematous changes and the relationship between irisin levels and CLAD after bilateral LDLLT and cadaveric lung transplantation (CLT)., Methods: The subjects of this retrospective study were 59 recipients of bilateral LDLLT (n = 31) or CLT (n = 28), divided into a non-CLAD group (n = 41), a LDLLT-CLAD group (n = 11), and a CLT-CLAD group (n = 7). We compared the severity of emphysematous changes, the skeletal muscle mass, and the plasma irisin levels among the groups., Results: The emphysematous changes were significantly more severe in the LDLLT-CLAD and CLT-CLAD groups (p = 0.046 and 0.036), especially in patients with bronchiolitis obliterans syndrome (BOS), than in the non-CLAD group. Although the skeletal muscle mass was similar in all the groups, the plasma irisin levels were significantly lower in the LDLLT-CLAD group (p = 0.022), especially in the patients with BOS after LDLLT, than in the non-CLAD group., Conclusion: Emphysematous changes and lower levels of plasma irisin were associated with CLAD, especially in patients with BOS, after bilateral LDLLT., (© 2021. Springer Nature Singapore Pte Ltd.)

Purpose: The effect of uniportal video-assisted thoracoscopic surgery (uni-VATS) versus that of conventional VATS on postoperative quality of life (QOL) is unclear. This prospective randomized controlled study compared uni-VATS and conventional 3-port VATS in terms of QOL and patient satisfaction., Methods: The subjects of this study were 84 patients with pulmonary nodules or bullous formation, randomized to undergo uniportal or conventional 3-port video-assisted thoracoscopic partial lung resection. The primary endpoint was postoperative pain, assessed using a numeric rating scale on postoperative day (POD) 1., Results: No differences were found in the numeric rating scale on POD 1 after uni-VATS and conventional 3-port VATS. There were also no differences in blood loss, operative time, complication rate, surgical margin, analgesic requirement, vital capacity (VC), forced expiratory volume in 1 s (FEV1), the 6-min walk test (6MWT), C-reactive protein (CRP) levels, white blood cell count (WBC), or duration of chest tube drainage and hospital stay. Differences were found in the numeric rating scale on days 2, 3, 5, and 10 and in the patient satisfaction score on PODs 5 and 10., Conclusions: Uni-VATS is associated with less chest pain and better patient satisfaction in the short term but without differences in complication rates or surgical margins from the lesions., Clinical Trial Registry Number: University Hospital Medical Information Network Clinical Trial Registry (UMIN000015340 http://www.umin.ac.jp/english/ )., (© 2021. Springer Nature Singapore Pte Ltd.)

Purpose: The prognostic nutritional index (PNI), calculated based on the serum albumin levels and the total lymphocyte count, has been identified as a predictor of clinical outcomes in various fields of surgery. In this study, we investigated the relationship between the PNI and the lung allocation score (LAS) as well as the impact of the PNI on the outcomes of both cadaveric lung transplantation (CLT) and living-donor lobar lung transplantation (LDLLT)., Methods: We reviewed retrospective data for 127 recipients of lung transplantation (LT), including 71 recipients of CLT and 56 recipients of LDLLT., Results: The PNI was correlated significantly and negatively with the LAS (r = - 0.40, P = 0.0000037). Multivariate analysis revealed that age (P = 0.00093), BMI (P = 0.00087), and PNI (P = 0.0046) were independent prognostic factors of a worse outcome after LT. In a subgroup analysis, survival after both CLT (P = 0.015) and LDLLT (P = 0.041) was significantly worse in the low PNI group than in the high PNI group., Conclusion: Preoperative nutritional evaluations using the PNI can assist with the assessment of disease severity in LT recipients and may predict survival after both CLT and LDLLT., (© 2021. Springer Nature Singapore Pte Ltd.)

Purpose: The number of elderly patients who undergo surgery is increasing, even though they are at a high risk due to a decreased physical strength. Furthermore, sarcopenia is generally associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC)., Methods: This study included NSCLC patients  ≥ 65 years old who underwent pulmonary resection in our hospital between 2012 and 2015. Sarcopenia was assessed using the psoas muscle mass index based on computed tomography at the level of the third lumbar vertebra. We elucidated the impact of sarcopenia on short- and long-term outcomes after surgery., Results: We enrolled 259 patients, including 179 with sarcopenia. Patients with sarcopenia before surgery tended to have postoperative complications (p = 0.0521), although they did not show a poor prognosis. In patients with sarcopenia, a multivariate analysis revealed that postoperative complications and the progression of sarcopenia 1 year after surgery were significant risk factors for a poor prognosis (p = 0.0169 and 0.00370, respectively)., Conclusions: The progression of sarcopenia after surgery is associated with a poor prognosis in elderly NSCLC patients with sarcopenia. A strategy to prevent postoperative progressive sarcopenia may be necessary for improving the clinical outcome of this population.

Purpose: The scheduled administration of intravenous acetaminophen (scheduled-IV-AcA) is one of the more effective multimodal analgesic approaches for postoperative pain in abdominal/orthopedic surgeries. However, there is little evidence concerning scheduled-IV-AcA after general thoracic surgery, especially when limited to video-assisted thoracoscopic surgery (VATS). We investigated the efficacy of scheduled-IV-AcA administration in patients after undergoing VATS., Methods: Ninety-nine patients who underwent VATS lobectomy or segmentectomy via an 8-cm access window and 1 camera port were retrospectively reviewed by categorizing them into groups either with scheduled-IV-AcA (Group AcA: n = 29) or without it (Group non-AcA: n = 70). Group AcA received 1 g of IV-AcA every 6 h from the end of the operation until the end of POD2. Postoperative pain was measured using a numeric rating scale (NRS) three times per day until discharge., Results: NRS scores were significantly lower in Group AcA with motion (on POD1 to the first point of POD2) than in Group non-AcA. Group non-AcA was also more likely to use additional analgesics than Group AcA (39% vs. 17%, p = 0.058)., Conclusions: Scheduled-IV-AcA administration is a safe and effective multimodal analgesic approach in patients undergoing VATS pulmonary resection via an 8-cm access window.

Purpose: Sarcomas are among the most refractory malignant tumors and often recur as pulmonary metastasis. Although the presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with the prognosis of several malignancies, the relationship between the NLR and sarcoma with pulmonary metastasis is unclear. We investigated the impact of the NLR in patients who underwent surgical resection for metastatic lung tumors from various sarcomas., Methods: The subjects of this retrospective study were 158 patients with metastatic lung tumors from various sarcomas, who underwent initial pulmonary metastasectomy between 2006 and 2015. We examined the clinicopathological variables, including the NLR and the characteristics of surgical procedures. Survival was estimated by the Kaplan-Meier method and prognostic factors were evaluated by multivariate analysis., Results: Multivariate analysis revealed significantly better survival of the group with an NLR < 2.26 immediately before the most recent pulmonary metastasectomy, in addition to such factors as the largest resected lesion being < 22 mm, a disease-free interval of > 2 years, and 3 or more pulmonary metastasectomies., Conclusion: The NLR immediately before the most recent pulmonary metastasectomy is a novel independent prognostic factor, which may be helpful when considering repeated pulmonary metastasectomy.

In patients with interstitial pneumonia, pulmonary fibrosis is an irreversible condition that can cause respiratory failure. Novel treatments for pulmonary fibrosis are necessary. Inflammation is thought to activate lung fibroblasts, resulting in pulmonary fibrosis. Of the known inflammatory molecules, we have focused on S100A8/A9 from the onset of inflammation to the subsequent progression of inflammation. Our findings confirmed the high expression of S100A8/A9 in specimens from patients with pulmonary fibrosis. An active role of S100A8/A9 was demonstrated not only in the proliferation of fibroblasts but also in the fibroblasts' differentiation to myofibroblasts (the active form of fibroblasts). S100A8/A9 also forced fibroblasts to upregulate the production of collagen. These effects were induced via the receptor of S100A8/A9, i.e., the receptor for advanced glycation end products (RAGE), on fibroblasts. The anti-S100A8/A9 neutralizing antibody inhibited the effects of S100A8/A9 on fibroblasts and suppressed the progression of fibrosis in bleomycin (BLM)-induced pulmonary fibrosis mouse model. Our findings strongly suggest a crucial role of S100A8/A9 in pulmonary fibrosis and the usefulness of S100A8/A9-targeting therapy for fibrosis interstitial pneumonia. HIGHLIGHTS: S100A8/A9 level is highly upregulated in the IPF patients' lungs as well as the blood. S100A8/A9 promotes not only the growth of fibroblasts but also differentiation to myofibroblasts. The cell surface RAGE acts as a crucial receptor to the extracellular S100A8/A9 in fibroblasts. The anti-S100A8/A9 antibody effectively suppresses the progression of IPF in a mouse model. In idiopathic pulmonary fibrosis (IPF), S100A8/A9, a heterodimer composed of S100A8 and S100A9 proteins, plays a crucial role in the onset of inflammation and the subsequent formation of a feed-forward inflammatory loop that promotes fibrosis. (1) The local, pronounced increase in S100A8/A9 in the injured inflammatory lung region-which is provided mainly by the activated neutrophils and macrophages-exerts strong inflammatory signals accompanied by dozens of inflammatory soluble factors including cytokines, chemokines, and growth factors that further act to produce and secrete S100A8/A9, eventually making a sustainable inflammatory circuit that supplies an indefinite presence of S100A8/A9 in the extracellular space with a mal-increased level. (2) The elevated S100A8/A9 compels fibroblasts to activate through receptor for advanced glycation end products (RAGE), one of the major S100A8/A9 receptors, resulting in the activation of NFκB, leading to fibroblast mal-events (e.g., elevated cell proliferation and transdifferentiation to myofibroblasts) that actively produce not only inflammatory cytokines but also collagen matrices. (3) Finally, the S100A8/A9-derived activation of lung fibroblasts under a chronic inflammation state leads to fibrosis events and constantly worsens fibrosis in the lung. Taken together, these findings suggest that the extracellular S100A8/A9 heterodimer protein is a novel mainstay soluble factor for IPF that exerts many functions as described above (1-3). Against this background, we herein applied the developed S100A8/A9 neutralizing antibody to prevent IPF. The IPF imitating lung fibrosis in an IPF mouse model was effectively blocked by treatment with the antibody, leading to enhanced survival. The developed S100A8/A9 antibody, as an innovative novel biologic, may help shed light on the difficulties encountered with IPF therapy in clinical settings.

Purpose: Trimodality therapy, comprised of induction chemoradiotherapy (iCRT) followed by surgery, is a highly invasive treatment option for locally advanced non-small cell lung cancers (LA-NSCLCs; defined as a heterogenous disease). We conducted this study to investigate the prognostic nutritional index (PNI) of LA-NSCLC patients undergoing trimodality therapy, which has not been studied in detail before., Methods: The subjects of this retrospective study were 127 patients who underwent trimodality therapy between 1999 and 2016. We measured the PNI at three points: before iCRT (pre-iCRT), before the operation, and after the operation., Results: PNIs decreased significantly as treatment progressed. Patients with clinical T3/4 (cT3/4) disease had a significantly lower PNI than those with cT1/2 disease, but the extent of lymph-node metastasis did not affect the PNI at any point. Using the cut-off values of receiver-operating curve analyses, multivariable analyses revealed that a high PNI pre-iCRT correlated significantly with a better survival of LA-NSCLC patients, especially those with cT3/4 disease (hazard ratio 3.84; 95% confidential interval 1.34-12.5, P = 0.012)., Conclusions: Measuring the PNI before trimodality therapy is important for predicting the clinical outcome of patients with LA-NSCLC, with differing predictive ability according to the disease extent. Perioperative intensive nutritional intervention must be considered for patients who undergo trimodality therapy for LA-NSCLC.

Purpose: Some long-term survivors after surgery for locally advanced non-small cell lung cancer (NSCLC) treated with induction chemoradiotherapy (trimodality treatment) develop chronic pulmonary aspergillosis (CPA). The aim of our study was to assess the characteristics and outcomes of CPA that develops after trimodality treatment., Methods: We retrospectively reviewed the data of 187 NSCLC patients who underwent trimodality treatment between 1999 and 2018., Results: Six male ever-smoker patients developed CPA. All 6 patients had undergone extended resection for NSCLC and had a history of either adjuvant chemotherapy (n = 3) or radiation pneumonitis (n = 4). Among the 4 patients with CPA localized in a single lung, 3 patients were treated surgically (completion pneumonectomy or cavernostomy) and 1 patient was treated with antifungal therapy alone. Both treatments led to the improved control of CPA. In contrast, patients with CPA in both lungs were not candidates for surgery, and died of CPA. The survival rates after trimodality treatment in the CPA group and the group without CPA were comparable (10-year survival rate, 50.0% vs. 57.6%, P = 0.59)., Conclusion: The early diagnosis of CPA localized in a single lung after NSCLC surgery is critical to improving control and survival in patients with CPA.

Purpose: The differences in chronic lung allograft dysfunction (CLAD) between living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT) remain unclear. We conducted this study to compare the impact of CLAD on the outcomes after LDLLT vs. CLT., Methods: We conducted a retrospective review of the data of 97 recipients of bilateral lung transplantation, including 51 recipients of LDLLT and 46 recipients of CLT., Results: The CLAD-free survival and overall survival after LDLLT were similar to those after CLT. CLAD and restrictive allograft syndrome (RAS), but not bronchiolitis obliterans syndrome (BOS), developed significantly later after LDLLT than after CLT (p = 0.015 and p = 0.035). Consequently, patients with CLAD and RAS, but not those with BOS, after LDLLT had a significantly better overall survival than those after CLT (p = 0.037 and p = 0.0006). Furthermore, after the diagnosis of CLAD, the survival of patients with RAS after LDLLT tended to be better than that after CLT (p = 0.083)., Conclusion: CLAD, especially RAS, appears to develop later after LDLLT than after CLT and seems to have a lower impact on the overall survival after LDLLT than that after CLT.

Purpose: Transfer of a free skin graft from the submalleolar or plantar instep area to the palmoplantar area and finger defects is widely performed; however, the sites and the border of plantar skin have yet to be examined in detail. The aim of this study was to determine the border of sole skin., Methods: Twelve paraformaldehyde-fixed cadavers were examined. Skin specimens were harvested from an area from the top of the medial malleolus extending to the top of the lateral malleolus of the right foot. The paraffin-embedded skin specimens were analyzed using histological (hematoxylin and eosin, Fontana-Masson, and elastica van Gieson stains) and immunohistochemical (cytokeratin 9) techniques., Results: CK9-positive cells were present at the points between 21 and 78 % of the intermalleolar distance measured from the tops of the medial and lateral malleoli. The melanin index abruptly changed at the points 25 ± 7.1 and 75 ± 4.2 %. The skin thickness and amount of elastic fibers changed greatly at the points between 20 and 30 % and between 70 and 80 % of the intermalleolar distance., Conclusions: Submalleolar skin is quite different from sole skin. The border of sole skin lies at the points between 20 and 25 % of the intermalleolar distance from the medial malleolus, which macroscopically corresponds to the border of skin maceration. It would be better to use the submalleolar area for grafts for the dorsum of the fingers or toes, and the plantar instep area for the ventral areas of the fingers or toes.

Purpose: Ischemia reperfusion injury (IRI) remains a significant cause of morbidity and mortality after lung transplantation. Early growth response-1 (EGR1) drives the expression of inflammatory mediators and has an important role in IRI. We hypothesized that the severe IRI caused by a long preservation induces a specific expression pattern of EGR1 and its target genes which would correlate with the lung graft function., Methods: SD rat lungs were preserved at 4 °C for 3 or 18 h, then transplanted and reperfused. Pulmonary grafts were evaluated for the blood gas oxygenation and pathological findings. The intra-graft mRNA levels of EGR1 and its downstream target genes were measured by real-time PCR. A Western blotting analysis of the EGR1 expression was used to validate the changes in the protein level., Results: There was upregulation of EGR1, MIP-2 and PAI-1 when there was prolonged hypothermic preservation. The expression levels of MIP-2 and PAI-1 were observed to increase for up to 4 h in the 18 h preserved lungs. There were no differences in the expression levels of IL-1β and ICAM-1 between the lungs subjected to short and long periods of ischemia., Conclusions: Our data showed that prolonged hypothermic graft preservation deteriorates the pulmonary graft function, which was associated with the induction of EGR1 and its downstream target genes, which may aggravate IRI following lung transplantation.

This report describes a new experimental procedure, a rat unilateral, orthotopic lung transplantation with cold storage, and evaluates its relevancy and reliability to study the early events during cold ischemia/reperfusion (I/R) injury. This model, using the cuff technique, does not require extensive training and is relatively easy to be established. The model can induce reproducible degrees of pulmonary graft injury including impaired gas exchange, proinflammatory cytokine upregulation, or inflammatory infiltrates, depending on the preservation time. The results are consistent with the previous clinical evidence, thus suggesting that this model is a valid and reliable animal model of cold I/R injury.

Purpose: To review the outcome of bronchial healing after living-donor lobar lung transplantation (LDLLT)., Methods: We retrospectively analyzed 87 anastomoses in 45 consecutive patients who underwent LDLLT, and 14 anastomoses in 10 consecutive patients who underwent cadaveric lung transplantation (CLT), between October 1998 and September 2007. Bronchial anastomosis complications that required intervention were defined as "airway complications" (ACs)., Results: There were no significant differences in the background characteristics of the LDLLT and CLT recipients. Airway complications developed in 2 (2.2%) of the 87 anastomoses in the LDLLT group and in 3 (21.4%) of the 14 anastomoses in the CLT group (P = 0.018). The donors of the LDLLT grafts were significantly younger than the donors of the CLT grafts (38.3 years vs 46.1 years, respectively; P = 0.013). The ischemic graft times in the LDLLT and CLT groups were 136.9 min and 413.7 min, respectively (P < 0.0001). The periods of pretransplant ventilation in the LDLLT and CLT groups were 0 days and 4.5 days, respectively (P = 0.0083)., Conclusion: Our study suggests that bronchial healing after LDLLT is acceptable.

Purpose: Living-donor lobar lung transplantation (LDLLT) is performed in critically ill patients, although the outcome is generally expected to be poor for those who are ventilator dependent. The aim of this study was to compare the outcomes of LDLLT in ventilator-dependent patients compared with those in ventilator-independent patients., Methods: We reviewed 31 consecutive patients who received LDLLT between October 1998 and May 2004., Results: Five patients were ventilator dependent and 26 were ventilator independent. All five ventilator-dependent patients were female, with a mean age of 29.6 years. The duration of preoperative ventilation was 23.4 +/- 5.7 days. The underlying diagnoses in the ventilator-dependent patients included only obstructive (n = 3) and infectious lung diseases (n = 2), whereas those in the ventilator-independent patients included hypertensive and restrictive diseases (P = 0.004). There were no significant differences between the groups in early postoperative clinical values. The incidences of acute rejection and bronchiolitis obliterans syndrome (BOS) were comparable. The 5-year survival rates were 100% for the ventilator-dependent patients and 92.3% for the ventilator-independent patients (P = 0.45)., Conclusion: Our findings suggest that LDLLT can have a favorable outcome in selected ventilator-dependent patients.

Hydrophobin cDNA (fv-hyd1), which is specifically expressed during fruiting body development, was isolated from the basidiomycete Flammulina velutipes by differential display screening. Analysis of the genomic structure of fv-hyd1 revealed an open reading frame (ORF) composed of 363 nucleotides and interrupted by three introns. The deduced amino acid sequence of FV-HYD1 showed a similarity to those of other fungal class I hydrophobins and contained eight cysteine residues highly conserved among hydrophobin proteins. The pattern of the hydropathy plot of FV-HYD1 was similar to those of class I hydrophobins. Southern blot analysis of genomic DNA showed that fv-hyd1 existed as a single copy. Northern blot analysis indicated that the fv-hyd1 transcript was not present in vegetative mycelia but markedly increased in level at the primordial stage. Moreover, the fv-hyd1 transcript was abundant even at the mature fruiting body stage. This result indicates that fv-hyd1 could encode a hydrophobin closely associated with fruiting body development.

A chitosanase was purified from the culture fluid of the chitino- and chitosanolytic bacterium Burkholderia gladioli strain CHB101. The purified enzyme (chitosanase A) had a molecular mass of 28 kDa, and catalyzed the endo-type cleavage of chitosans having a low degree of acetylation (0-30%). The enzyme hydrolyzed glucosamine oligomers larger than a pentamer, but did not exhibit any activity toward N-acetylglucosamine oligomers and colloidal chitin. The gene coding for chitosanase A (csnA) was isolated and its nucleotide sequence determined. B. gladioli csnA has an ORF encoding a polypeptide of 355 amino acid residues. Analysis of the N-terminal amino acid sequence of the purified chitosanase A and comparison with that deduced from the csnA ORF suggests post-translational processing of a putative signal peptide and a possible substrate-binding domain. The deduced amino acid sequence corresponding to the mature protein showed 80% similarity to the sequences reported from Bacillus circulans strain MH-K1 and Bacillus ehimensis strain EAG1, which belong to family 46 glycosyl hydrolases.

Duodenal varices are a rare site of hemorrhage in patients with portal hypertension, but their rupture is a serious and often fatal event. We report a 65-year-old woman who presented with hematemesis and melena. She was admitted to our department because of prolonged shock, despite having received transfusion of a large volume of blood. Upper gastrointestinal endoscopy revealed nodular varices with active bleeding in the second portion of the duodenum. Endoscopic injection sclerotherapy (EIS) was performed using a tissue adhesive agent, alpha-cyanoacrylate monomer, with only temporary benefit. However, anemia continued to progress after the procedure. Therefore, we combined transileocolic vein obliteration (TIO) with balloon-occluded retrograde transvenous obliteration (B-RIO), using 5% ethanolamine oleate with iopamidol to obliterate the varices. Complete hemostasis was achieved without complications. Neither recurrence of varices nor further bleeding has occurred for over 3 years. We conclude that combined TIO and B-RTO, which can obstruct both the feeding and the draining vessels of duodenal varices to retain the sclerosing agent completely in the varices, is a safe and effective hemostatic measure for ruptured duodenal varices, when EIS has failed to accomplish complete hemostasis.

We present our clinical experience with dynamic contrast-enhanced MR angiography (MRA) with subtraction for assessing intracranial vascular abnormalities. Ten patients with various cerebrovascular disorders underwent dynamic contrast-enhanced MRA on a 1.0-T system. Thirty sections (2 mm) were acquired in 29-30 s. Maximum intensity projection images and subtracted source images were compared with those obtained by conventional angiography. In all cases, the presence or absence of abnormalities in the targeted vessels, as well as the morphology of the sagittal sinuses, was clearly visualized as in conventional angiography, without any obstructions such as hyperintense hematomas or thrombi, or intraluminal turbulence. Although the temporal and spatial resolutions with current hardware are insufficient, these preliminary results suggest that dynamic contrast-enhanced MRA with subtraction may be useful for assessing vascular lesions with hemorrhage or thrombus, and the dural sinuses.

Nipple discharge disorders is a field in which there has been both increasing awareness on the part of patients and advances in management. Today secretion from nipples can be classified according to its color, cellularity and biology. To be significant a discharge should be true, spontaneous, persistent and non-lactational. Moreover there are methods to differentiate patients who require surgical intervention from those who do not. Surgically significant nipple discharges are watery, serous (yellow), serosanguineous and bloody. Cytology smears of discharge material have helped to classify the cellular material, providing information about normality, atypia and malignancy and also about papillary formation of the exfoliated cells. Tests such as Hemoccult help to discover occult blood in the secreted fluid. Modern immunological tests can be performed on cytology smears where occurrence of high levels of carcinoembryonic antigen could indicate a latent malignancy. Galactography investigation is today the state-of-the-art approach to investigate patients with nipple discharge disorders and this examination can demonstrate the size, location and extent of an intraductal abnormality. Modern high-resolution ultrasound techniques are helpful in visualizing intraductal disorders and are becoming a good complementary approach if not an alternative to traditional radiology techniques. Recently even MR galactography has been shown to be of diagnostic value, but not as informative as regular galactography. The most sophisticated investigation method, which can also be used therapeutically, is fiber-ductoscopy of the concerned duct in a breast. This technique, although expensive and in its infancy, is a fascinating and promising approach for inspecting the intraductal lumina. In this article the background, current investigation methods and possibilities of the technique are described, as well as the most sophisticated ways to deal with nipple discharge disorders in human breasts.

We report on a 71-year old man with hepatocellular carcinoma (HCC) whose obstructive jaundice was successfully treated with external irradiation and a self-expandable metallic stent (EMS); Wallstent; Schneider (Europe) AG, Bülach, Switzerland. He was admitted to our hospital because of jaundice. HCC was found in S8; the tumor had invaded the bile duct with growth in the common hepatic duct. Endoscopic nasobiliary drainage was performed with difficulty. Radiation therapy to the stenosis enabled us to place a Wallstent endoscopically. He survived without icterus for 1 year.

Duodenal varices are a rare site of hemorrhage in patients with portal hypertension, but their rupture is a serious and often fatal event. We report the case of a 77-year-old woman with cirrhosis who presented with melena. She was admitted to our Department because of prolonged shock although she had received a large blood transfusion. Upper gastrointestinal endoscopy revealed nodular varices in the third portion of the duodenum which were considered to be the source of the bleeding. Endoscopic injection sclerotherapy (EIS) with n-butyl-2-cyanoacrylate (Histoacryl; Braun-Melsungen, Germany), an adhesive agent, was performed. We injected 1.5 ml of Histoacryl with Lipiodol (Laboratoire-Guerbet, France) intravariceally and achieved successful hemostasis. This patient's duodenal varices had almost completely resolved 1 month after EIS. We conclude that EIS with Histoacryl is an effective hemostatic measure for ruptured duodenal varices.

To evaluate the effects of intraarterial infusion chemotherapy (IAIC) for advanced breast cancer, we examined the grade of histological responses of preoperative IAIC on tumors at the time of operation and estimated the patients' prognoses for 19 years. IAIC was done preoperatively using timely epochal anticancer drugs on 105 patients with locally advanced (Stage IIIa, IIIb) and metastatic (Stage IV) breast cancer. The survival rate of the Stage IIIb patients who showed a good histological response (Grade IIb< or =) to IAIC was 68.1% for 5 years, and 62.4% for 10 years, respectively. This was in contrast to that of the patients classified as Stage IIIb who showed a poor histological response (Grade IIa> or =) to IAIC. On the other hand, there was no significant difference in the survival rates between the Stage IIIa and IV patients with good and poor histological responses to IAIC. However, the findings showed that a good histological response to IAIC reflected a prolonged survival while the Stage IIIb and IV patients acquired a "down clinical staging" by IAIC. These results strongly suggest that IAIC thus appears to be a useful modality in the multidisciplinary treatment of advanced breast cancer, especially for Stage IIIb patients.

The correlation between serum hepatitis C virus (HCV)-RNA and aminotransferase levels following completion of interferon therapy was evaluated in eight relapsed patients with chronic hepatitis C. Both HCV-RNA and aminotransferase levels were significantly increased in the relapsed patients 1 month after completion of therapy, compared to pretreatment values, despite aminotransferase levels being normal and HCV-RNA being undetectable by reverse transcription polymerase chain reaction assay at the end of therapy. The serum levels of HCV-RNA and aminotransferase were significantly elevated 1 and 2 months post-treatment. They then decreased to pretreatment values 3-5 months after the completion of therapy. Thus, in relapsed patients after the completion of therapy, the changes in HCV-RNA levels preceded the elevation in aminotransferase levels. These findings suggest a correlation between serum HCV-RNA levels and aminotransferase levels in relapsed patients with chronic hepatitis C after the completion of interferon therapy.

Angiographic findings of the vitelline artery in five patients with surgically proven Meckel's diverticulum were reviewed retrospectively. Superselective vitelline arteriography was performed in two patients and superior mesenteric arteriography in three. Arteriography showed the elongated artery without branching originating from the distal ileal artery and a group of tortuous vessels at the distal portion of this artery in all patients. A dense capillary staining of the vitelline artery was exclusively shown in patients with ectopic gastric mucosa. In one patient, injection of methylene blue intraoperatively through a previously placed angiographic catheter into the vitelline artery stained only the vitelline artery and Meckel's diverticulum in blue but neither the mesentery nor the ileum. Demonstration of a nonbranching artery from the ileal artery and a group of dilated tortuous vessels at the distal portion of this artery should suggest the possibility of Meckel's diverticulum and can be confirmed by selective injection of the artery. It should be emphasized that angiography can detect Meckel's diverticulum even in the absence of acute bleeding.

A 68-year-old man with the clinical features of Cronkhite-Canada syndrome developed cancer of the ascending colon. Although Cronkhite-Canada syndrome has always been considered a benign condition, it may be a premalignant disorder, as suggested by the clinical course of the patient whose case is described herein.