Supraglottic myxoedema successfully treated orally.

Summary: Myxoedema coma is a severe form of hypothyroidism with multiple organ dysfunction, characterised by an altered state of consciousness and hypothermia. Intravenous thyroid hormone replacement therapy is the preferred treatment for myxoedema. The mortality rate associated with this disease is high, and early detection and intervention are essential. Supraglottal myxoedema is a rare form of periglottic oedema and can be fatal. A previously healthy 66-year-old man presented with impaired consciousness, hypothermia, and nonpitting oedema. Blood tests revealed the presence of hypothyroidism and respiratory acidosis. He was intubated for type 2 respiratory failure; however, severe laryngeal oedema made the procedure difficult to perform. Oral thyroid hormone therapy was initiated under the diagnosis of myxoedema coma. Tracheostomy was performed because of prolonged type 2 respiratory failure and laryngeal oedema. Three weeks after admission, the patient was weaned off the ventilator. Approximately a week later, laryngeal oedema improved, and the tracheostomy tube was removed. The patient was discharged and remained stable for 3 months. This case report describes a patient with comatose myxoedema and supraglottic oedema who was successfully treated with oral medication alone. This case shows that supraglottic oedema should be considered even in the absence of wheezing or other signs of upper airway obstruction. Learning points: Myxoedema coma is a differential diagnosis of respiratory acidosis. In myxoedematous coma, the possibility of difficult intubation due to supraglottic oedema should be considered. Tracheostomy should be considered for supraglottic myxoedema, which often results in prolonged ventilator use. Supraglottic myxoedema can be treated with oral medications.

Atypical presentation of tight filum terminale with thoracic disc herniation: a case report.

BACKGROUND: Tight filum terminale is a rare and challenging condition to diagnose because it presents with nonspecific symptoms and unclear imaging findings. This report documents an atypical case of tight filum terminale. CASE PRESENTATION: The patient was a previously healthy Asian 18-year-old male presenting with recurrent upper extremity and back pain, initially treated as nonspecific musculoskeletal pain. Notably, the patient's symptoms were inconsistent with the dermatome, showing no correlation with his skin's sensory innervation areas. In contrast to typical tight filum terminale presentations focused on lower extremity and lumbar region disturbances, this patient experienced pain and weakness predominantly in the upper extremities and back, hypothesized to result from traction myelopathy exacerbated by thoracic disc herniation. Investigations including blood and nerve function tests were inconclusive. However, a magnetic resonance imaging scan revealed a combination of tight filum terminale and tiny thoracic disc herniation. A diagnosis of tethered spinal cord syndrome was confirmed following further tests and imaging. The filum terminale was surgically removed, resolving the symptoms at a 7-month follow-up. CONCLUSIONS: This case underlines the importance of including tight filum terminale as a differential diagnosis in cases of unexplained upper or lower extremity pain. Primary care practitioners, particularly those managing undefined symptoms, should consider tight filum terminale in their diagnostic approach.

Non-stapling thoracoscopic surgery for spontaneous pneumothorax in young patients.

OBJECTIVES: Spontaneous pneumothorax in young patients has a high recurrence rate, even after surgical treatment, and bulla neogenesis around stapled lesions has been reported as a cause of postoperative recurrence. We investigate the clinical safety and long-term outcome of non-stapling thoracoscopic surgery for spontaneous pneumothorax in young patients. METHODS: Twenty-seven non-stapling thoracoscopic surgeries for pneumothorax in 24 patients younger than 25 years were retrospectively reviewed. The non-stapling surgical techniques used to treat bullae included thoracoscopic suture plication, soft-coagulation, covering, and ligation. Long-term follow-up was conducted by telephone or by a mailed questionnaire. RESULTS: In 22 (81.5%) operations, suture plication, soft-coagulation, and covering procedures were used in combination. The median number of bullae treated in one operation was 2 (range, 0-6). The median operative time was 97 min, and the median postoperative drainage and postoperative hospital stay periods were 1 and 3 days, respectively. No complications of grade 2 or higher were observed. Patients were followed for at least 30 (median, 37) months. The postoperative recurrence rate was 3.7%, with one case of recurrence due to bulla neogenesis at a distant site. CONCLUSION: Non-stapling thoracoscopic surgery with covering procedure for pneumothorax in young patients might reduce postoperative recurrence.

Proteomic analysis identifies argininosuccinate synthetase 1 and special AT-rich sequence binding protein 1 as reliable markers for the immunohistochemical distinction between WHO types A and B3 thymomas.

AIMS: The reliable classification of type A versus type B3 thymomas has prognostic and therapeutic relevance, but can be problematic due to considerably overlapping morphology. No immunohistochemical markers aiding in this distinction have been published so far. METHODS AND RESULTS: We identified and quantified numerous differentially expressed proteins using an unbiased proteomic screen by mass spectrometry in pooled protein lysates from three type A and three type B3 thymomas. From these, candidates were validated in a larger series of paraffin-embedded type A and B3 thymomas. We identified argininosuccinate synthetase 1 (ASS1) and special AT-rich sequence binding protein 1 (SATB1) as highly discriminatory between 34 type A and 20 type B3 thymomas (94% sensitivity, 98% specificity and 96% accuracy). Although not the focus of this study, the same markers also proved helpful in the diagnosis of type AB (n = 14), B1 (n = 4) and B2 thymomas (n = 10). CONCLUSIONS: Mutually exclusive epithelial expression of ASS1 in 100% of type B3 thymomas and ectopic nuclear expression of SATB1 in 92% of type A thymomas support the distinction between type A and type B3 thymomas with 94% sensitivity, 98% specificity and 96% accuracy.

Characteristic differences in the abundance of tumor-infiltrating lymphocytes and intratumoral developing T cells in thymoma, with special reference to PD-1 expression.

PURPOSE: Though programmed cell death-1 (PD-1) inhibitors mainly target tumor-infiltrating lymphocytes (TILs) expressing PD-1, developing T cells in thymus also express PD-1 in their process of maturation. To predict the therapeutic effect of PD-1 inhibitors for thymoma, it is necessary to clarify the proportions of TILs and intratumoral developing T cells. METHODS: The expressions of CD4, CD8, and PD-1 on T cells were analyzed by flow cytometry in 31 thymomas. The amount of T cell receptor excision circles (TRECs), which can be detected in newly formed naïve T cells in the thymus, was evaluated using sorted lymphocytes from thymomas by quantitative PCR. The expressions of granzyme B (GZMB) and lymphocyte activation gene-3 (LAG-3) in PD-1 + CD8 T cells were analyzed by image cytometry using multiplex immunohistochemistry. RESULTS: The PD-1 + rate in both CD4 and CD8 T cells was significantly higher in type AB/B1/B2 than in type A/B3 thymomas. The amounts of TRECs in CD4 and CD8 T cells were significantly higher in type AB/B1/B2 than in type A/B3 thymomas and comparable to normal thymus. PD-1 expression at each stage of T cell development of type AB/B1/B2 thymomas was comparable to that of normal thymus. Both the percentages and cell densities of PD-1 + CD8 T cells expressing GZMB or LAG-3, which are known to contain tumor-reactive T cells, were significantly lower in type AB/B1/B2 thymomas. CONCLUSION: Most PD-1 + T cells in type AB/B1/B2 thymomas are intratumoral developing T cells and are not TILs.

Usefulness of free pericardial fat pads as pledgets for air leaks in pulmonary resection.

PURPOSE: Intraoperative control of air leaks is important for preventing prolonged air leaks after surgery. The usefulness of suturing free pericardial fat pads (FPFPs) as pledgets for repairing air leaks was investigated. METHODS: A total of 111 patients who underwent anatomical lung resection and required suture repair for intraoperative air leaks were retrospectively reviewed. Mattress sutures were performed using polyglycolic acid (PGA) sheets (PGA group; n = 60) in the early period (April 2014 to March 2018) and FPFPs (FPFP group; n = 51) in the late period (April 2018 to March 2021) as pledgets. RESULTS: More patients had a history of smoking in the FPFP group than in the PGA group. The duration of air leakage was significantly shorter (mean 1.2 vs. 3.5 days, p = 0.002) and prolonged air leakage (> 5 days) was less frequently observed (23.3% vs. 5.9%, p = 0.016) in the FPFP group than in the PGA group. The FPFP group had fewer cases requiring pleurodesis and with recurrent air leaks than in the PGA group. In one case in the FPFP group, fat necrosis with fibrosis and fibrous adhesion to the visceral pleura was found on a pathological examination. CONCLUSION: Parenchymal repair using FPFPs as pledgets can reduce prolonged air leaks after surgery.

Spread through air spaces is a powerful prognostic predictor in patients with completely resected pathological stage I lung adenocarcinoma.

PURPOSE: To evaluate the frequency of spread through air spaces (STAS) in patients with early-stage primary lung cancer and to elucidate the association between STAS and various clinicopathological factors. METHODS: We retrospectively reviewed data from a total of 265 consecutive patients who underwent lobectomy and mediastinal lymph node dissection (172 patients) or sublobar resection (93 patients) for completely resected pathological stage I lung adenocarcinoma. We evaluated clinical variables, including the preoperative serum carcinoembryonic antigen (CEA) level, tumour size, consolidation tumour ratio (CTR), maximum standardized uptake value (SUVmax) on FDG-PET, histological results, presence of STAS and vascular and lymphatic invasion. RESULTS: The median follow-up time after surgery was 49 months. Eighty-seven patients (32.8 %) had STAS. The overall survival rates of patients in the STAS-positive and STAS-negative groups were 92.7 % and 97.1 % at 3 years, respectively (p = 0.1255), and the recurrence-free survival rates were 82.1 % and 95.9 % at 3 years, respectively (p = 0.0001). STAS was found in 73 patients (42.4 %) in the lobectomy group, which was a significantly higher proportion than the 14 patients (15.1 %) in the sublobar resection group. The STAS-positive group had significantly larger areas of invasion, higher CTRs, preoperative CEA and SUVmax levels, and more lymphatic and vascular invasion. STAS also correlated significantly with large consolidation sizes, larger invasive size, higher CTRs and the presence of a micropapillary pattern. Cox regression analysis after adjustment for important prognostic factors revealed that the presence of STAS was an independent predictor associated with postoperative recurrence, most of which was observed locoregionally. CONCLUSIONS: STAS was an independent factor associated with postoperative recurrence after lung resection for stage I lung adenocarcinoma. Among stage IA patients, the postoperative outcomes of STAS-positive patients were worse than those of STAS-negative patients and were similar to those of stage IB patients.

Phosphoproteomic Analysis Identifies TYRO3 as a Mediator of Sunitinib Resistance in Metastatic Thymomas.

BACKGROUND: After initially responding to empiric radio-chemotherapy, most advanced thymomas (TH) and thymic carcinomas (TC) become refractory and require second-line therapy. The multi-target receptor tyrosine kinase (RTK) inhibitor, sunitinib, is one of the few options, especially in patients with thymic carcinomas, and has resulted in partial remissions and prolonged overall survival. However, sunitinib shows variable activity in thymomas, and not all patients benefit equally. A better understanding of its mode of action and the definition of predictive biomarkers would help select patients who profit most. METHODS: Six cell lines were treated with sunitinib in vitro. Cell viability was measured by MTS assay and used to define in vitro responders and non-responders. A quantitative real-time assay simultaneously measuring the phosphorylation of 144 tyrosine kinase substrates was used to correlate cell viability with alterations of the phospho-kinome, calculate a sunitinib response index (SRI), and impute upstream tyrosine kinases. Sunitinib was added to protein lysates of 29 malignant TH and TC. Lysates were analyzed with the same phosphorylation assay. The SRI tentatively classified cases into potential clinical responders and non-responders. In addition, the activation patterns of 44 RTKs were studied by phospho-RTK arrays in 37 TH and TC. RESULTS: SRI application separated thymic epithelial tumors (TET) in potential sunitinib responders and resistant cases. Upstream kinase prediction identified multiple RTKs potentially involved in sunitinib response, many of which were subsequently shown to be differentially overexpressed in TH and TC. Among these, TYRO3/Dtk stood out since it was exclusively present in metastatic TH. The function of TYRO3 as a mediator of sunitinib resistance was experimentally validated in vitro. CONCLUSIONS: Using indirect and direct phosphoproteomic analyses to predict sunitinib response in malignant TET, we have shown that TH and TC express multiple important sunitinib target RTKs. Among these, TYRO3 was identified as a potent mediator of sunitinib resistance activity, specifically in metastatic TH. TYRO3 may thus be both a novel biomarker of sunitinib resistance and a potential therapeutic target in advanced thymomas and thymic carcinomas.

Prognostic Impact of Using Combined Plasma Fibrinogen Level and Neutrophil-to-Lymphocyte Ratio in Resectable Non-small Cell Lung Cancer.

BACKGROUND: Both plasma fibrinogen level and neutrophil-to-lymphocyte ratio (NLR) are associated with malignant potential in different cancer types. The current study evaluated the use of combined plasma fibrinogen level and NLR (F-NLR) as a prognostic predictor in patients with non-small cell lung cancer (NSCLC). METHODS: Data collected from 279 patients with resectable NSCLC were retrospectively reviewed. Patients were divided into three groups based on the F-NLR score: score 2, high fibrinogen level (≥350 mg/dL) and high NLR (≥2.5); score 1, either high fibrinogen level or high NLR; and score 0, neither abnormal. Overall survival (OS) and relapse-free survival (RFS) were evaluated using the Kaplan-Meier method and log-rank test. Cox proportional hazard model was used to assess prognostic factors. RESULTS: Numbers of patients with F-NLR score of 0, 1, and 2 were 122 (43.7%), 105 (37.6%), and 52 (18.6%), respectively. The F-NLR was found to be significantly associated with age, male sex, heavy smoking history, high pT status and pathological stage, and nonadenocarcinoma. Moreover, the OS and RFS significantly differed according to the F-NLR score (P < 0.001, P = 0.003). A multivariate analysis revealed that a high F-NLR score (≥1) was an independent poor prognostic factor for OS (P = 0.027). In subgroup analyses, an adverse prognostic impact of the F-NLR score on OS was identified regardless of nodal involvement or pathological stage. CONCLUSIONS: The F-NLR score, which is based on histological inflammation and coagulability, could be a potential prognostic indicator in patients with resectable NSCLC.

Clinical significance of postoperative pulmonary complications in elderly patients with lung cancer.

OBJECTIVES: An increasing number of elderly patients with impaired immunity, malnutrition and comorbidities are considered surgical candidates. This study aimed to clarify the predictive factors and prognostic impact of postoperative pulmonary complications in elderly patients with lung cancer. METHODS: This retrospective study included 188 patients (≥75 years) who underwent complete anatomical lung resection for non-small cell lung cancer between 2005 and 2019. Postoperative pulmonary complications graded ≥II in the Clavien-Dindo classification, occurring within 30-day post-surgery were evaluated. Multivariate logistic regression analyses and Cox proportional hazard models were used to analyse predictors and prognostic impact of complications. RESULTS: Video-assisted thoracoscopic surgery was performed in 154 patients (81.9%). The 90-day mortality rate was 0.5%. Postoperative pulmonary complications including air leak, pneumonia, sputum retention, atelectasis, bronchopleural fistula and empyema occurred in 29 patients (15.4%). A lower prognostic nutritional index (<45) and longer operative time were independent predictive factors of pulmonary complications, with 33.3% of patients experiencing both factors. Following a median follow-up of 48 months, the 5-year overall and relapse-free survival rates were significantly worse in patients with pulmonary complications than in those without them (54.4% vs 81.5% and 41.2% vs 74.9%). Pulmonary complications were significantly associated with worse overall and relapse-free survival [hazard ratio (95% confidence interval): 1.97 (1.01-3.66), P = 0.047 and 2.35 (1.28-4.12), P = 0.007, respectively] along with pathologic stage and carcinoembryonic antigen levels. CONCLUSIONS: Postoperative pulmonary complications are associated with a lower prognostic nutritional index and prolonged operative time; the complications are independent adverse prognostic factors in elderly patients.

Robotic subxiphoid-optical thymectomy.

Robot-assisted thymectomy through a subxiphoid scopic approach can provide a good surgical view, similar to that of median sternotomy. We originally used the subxiphoid port only for the robotic scope to avoid instrument collision with the assistant device. This approach, robotic subxiphoid-optical thymectomy, is advantageous for the safe and accurate dissection of the bilateral phrenic nerves and the left brachiocephalic vein, which are especially needed in extended thymectomy for patients with myasthenia gravis.

Temperature dependence of amorphous magnesium carbonate structure studied by PDF and XAFS analyses.

Mineral trapping through the precipitation of carbonate minerals is a potential approach to reduce CO2 accumulation in the atmosphere. The temperature dependence of amorphous magnesium carbonate (AMC), a precursor of crystalline magnesium carbonate hydrates, was investigated using synchrotron X-ray scattering experiments with atomic pair distribution function (PDF) and X-ray absorption fine structure analysis. PDF analysis revealed that there were no substantial structural differences among the AMC samples synthesized at 20, 60, and 80 °C. In addition, the medium-range order of all three AMC samples was very similar to that of hydromagnesite. Stirring in aqueous solution at room temperature caused the AMC sample to hydrate immediately and form a three-dimensional hydrogen-bonding network. Consequently, it crystallized with the long-range structural order of nesquehonite. The Mg K-edge X-ray absorption near-edge structure spectrum of AMC prepared at 20 °C was very similar to that of nesquehonite, implying that the electronic structure and coordination geometry of Mg atoms in AMC synthesized at 20 °C are highly similar to those in nesquehonite. Therefore, the short-range order (coordination environment) around the Mg atoms was slightly modified with temperature, but the medium-range order of AMC remained unchanged between 20 and 80 °C.

Extrathoracic Superior Vena Cava Bypass With Venous Return Cannulas in Malignant Mediastinal Tumor Surgery.

Combined resection of the superior vena cava is sometimes challenging during radical surgery for malignant mediastinal tumors. We report a case of a 21-year-old man with a malignant mediastinal germ cell tumor who underwent surgical resection with superior vena cava reconstruction involving an extrathoracic temporary bypass from the right brachiocephalic vein to the right atrium using a venous return cannula because of left brachiocephalic vein occlusion. This is a convenient and safe optional technique providing an excellent intrathoracic surgical view for temporary superior vena cava bypass in patients with invasive malignant mediastinal tumor associated with venous return through the hemilateral brachiocephalic vein.

HSP110 expression in canine mammary gland tumor and its correlation with histopathological classification and grade.

Heat shock proteins (HSPs) play critical roles as molecular chaperones, thereby promoting cellular homeostasis. HSPs are overexpressed in many types of human tumors and their serum concentration is elevated in cancer patients. Recent studies have suggested that HSPs may promote tumorigenesis via interactions with tumor-related proteins. There are only a few studies that address the expression of HSPs in canine tumors. In our previous study, we identified elevated levels of HSP110 expression in canine mammary gland tumors (cMGTs). In this study, we examined both serum concentrations and tissue expression of HSP110 in dogs with cMGT. We found that serum HSP110 concentrations were not significantly different in a comparison between dogs with cMGT (3.44 ± 1.27 µg/mL) and healthy controls (3.23 ± 1.18 µg/mL). By contrast, significant differences in levels of HSP110 expression were identified in comparisons between simple carcinoma and benign mixed tumor (p = 0.001), simple carcinoma and non-neoplastic lesions (p < 0.001), complex carcinoma and benign mixed tumor (p = 0.015), complex carcinoma and non-neoplastic lesions (p < 0.001), simple adenoma and benign mixed tumor (p = 0.041), and simple adenoma and non-neoplastic lesions (p = 0.007). Similarly, significantly different levels of HSP110 expression were identified when comparing grade Ⅲ with non-neoplastic lesion (p = 0.026), grade Ⅱ with benign tumor (p = 0.015), grade Ⅱ with non-neoplastic lesion (p < 0.001), and grade Ⅰ with non-neoplastic lesion (p < 0.001). Taken together, our results indicate that expression of HSP110 correlates with the malignancy in this cohort of dogs diagnosed with cMGT. These findings also suggest that HSP110 is associated with tumorigenesis and the relative malignancy of cMGT.

Prognostic value of visceral pleural invasion in pure-solid and part-solid lung cancer patients.

OBJECTIVE: Visceral pleural invasion (VPI) indicates poor prognosis in non-small cell lung cancer (NSCLC), and is defined as a T2 descriptor for T1-sized tumor. However, whether its prognostic impact differs between pure-solid and part-solid tumors as preoperative diagnostic imaging is controversial. We aimed to elucidate the prognostic difference of VPI in cT1-sized NSCLC according to radiological tumor type (pure-solid or part-solid). METHODS: We retrospectively reviewed 498 NSCLC patients who underwent complete anatomical lung resection between 2009 and 2014. Patients with node-negative, cT1-sized (consolidation size, ≤ 3 cm) NSCLCs were included. VPI included pathological PL1 and PL2. The prognostic impact of VPI according to radiological tumor type was assessed using multivariate Cox regression analyses. RESULTS: We evaluated 227 pure-solid and 271 part-solid tumors; median follow-up period was 57 months. VPI was found in 40 (17.6%) and 15 (5.5%) patients with pure-solid and part-solid tumors, respectively (p < 0.001). In pure-solid group, VPI patients showed significantly poorer overall survival (OS) rates than non-VPI patients (p = 0.003). In part-solid group, OS rates did not differ significantly according to VPI (p = 0.770). Multivariate analysis revealed that the adjusted hazard ratio (95% confidence interval) for poor OS was 2.129 (1.048-4.132, p = 0.037) for pure-solid tumors with VPI compared to pure-solid tumors without VPI, and 0.925 (0.050-4.920, p = 0.941) for part-solid tumors with VPI compared to part-solid tumors without VPI. CONCLUSIONS: VPI had a negative prognostic impact on cT1-sized pure-solid tumors but not on part-solid tumors. Upstaging of the T-category by VPI in cT1-sized NSCLCs may be considered for pure-solid tumors.

TTF-1 and c-MYC-defined Phenotypes of Large Cell Neuroendocrine Carcinoma and Delta-like Protein 3 Expression for Treatment Selection.

The standard treatment regimen has not yet been established for advanced pulmonary large cell neuroendocrine carcinoma (LCNEC) because of its rarity. LCNEC can be subdivided into 2 mutually exclusive molecular subgroups: STK11/KEAP1 and TP53 mutated with high neuroendocrine expression and transcriptional profile of ASCL1high/DLL3high/NOTCHlow (non-small cell lung carcinoma, NSCLC-like) or RB1 and TP53 mutated with reduced neuroendocrine markers and transcriptional pattern of ASCL1low/DLL3low/NOTCHhigh (small cell lung cancer, SCLC-like). Model-based clustering shows that SCLC has subdivided into 2 major proteomic subsets defined by either TTF-1high/c-MYClow or TTF-1low/c-MYChigh, which may correspond to 2 mutually exclusive molecular subgroups: NSCLC-like or SCLC-like, respectively. We herein investigated whether TTF-1 and c-MYC could be applied to LCNEC to identify distinct subsets immunohistochemically and assessed DLL3 expression in these subsets. The protein expression profile may be useful to select patients for potential efficacy of targeted therapies including aurora kinase inhibitors for MYC alterations or anti-DLL3 antibody-drug conjugates. TTF-1 and c-MYC expression was mutually exclusive in 25 of 27 (93%) cases; TTF-1+/c-MYC- in 10, TTF-1-/c-MYC+ in 15, and TTF-1+/c-MYC+ in 2. DLL3 expression was seen in 15 of 27 cases (56%). All 12 TTF-1+ LCNEC cases were positive for DLL3. Three of 15 (20%) TTF-1-/c-MYC+ cases showed DLL3 positivity. LCNEC could be separated into 2 subsets proteomically defined by TTF-1 and c-MYC expression, which may be suitable to guide treatment selection including aurora kinase inhibitors for c-MYC+ cases. TTF-1 positivity can serve as a surrogate marker for DLL3, but caution is necessary as 20% of TTF-1- cases showed DLL3 positivity.

External Corset Technique in a Patient With Anomalous Artery Supply to the Left Basal Segment.

Postoperative aneurysmal formation of the anomalous artery stump has been reported in the systemic arterial supply to the basal segment of the left lung, whereas the effective preventive strategy remains unclear. Herein we report a case successfully treated with a new external corset technique of an anomalous artery stump. A 54-year-old man with a history of repeated hemoptysis underwent a left lower lobectomy. The anomalous artery stump with a 1.1 cm diameter was wrapped using woven Dacron vascular graft. No aneurysmal change has been observed in the computed tomography obtained after 3 years of follow-up.

Prognostic significance of spread through air spaces in pulmonary metastases from colorectal cancer.

OBJECTIVES: Surgical resection for pulmonary metastases from colorectal cancer could provide long-term survival in selected patients, and it is commonly performed in practice. However, surgical margin relapse sometimes occurs and is a problematic issue to resolve. Spread through air spaces (STAS) is one of the invasion forms in primary lung cancer and is associated with local recurrence and a poor prognosis. The aim of this study was to evaluate the prognostic significance of STAS for pulmonary metastases from colorectal cancer and to assess the predictability of STAS with preoperative clinical information. METHODS: A total of 96 pulmonary metastatic lesions from colorectal cancer in 37 patients who underwent metastasectomy at our institution from January 2008 to December 2013 were retrospectively analyzed. RESULTS: STAS was identified in 41.6 % of the 96 lesions. Surgical margin relapse was found in 8 lesions (8.3 %) from 7 patients (18.9 %). The distance of STAS was identified as an independent risk factor for surgical margin relapse on multivariable analysis (p =  0.033). The patients with STAS showed significantly worse overall survival than those without (5-year overall survival rate: 30.3 % vs. 76.9 %; p =  0.002). On multivariable analysis, patients with STAS had a significantly higher risk of death than those without (p =  0.019). An elevated pre-metastasectomy serum carcinoembryonic antigen level was independently correlated with STAS on multivariable analysis (p =  0.049). CONCLUSION: STAS was related to a poor prognosis and surgical margin relapse in pulmonary metastases from colorectal cancer.

One-stage closure of large bronchopleural fistula with pedicled latissimus dorsi muscle flap after preemptive antibiotics: A case report.

INTRODUCTION: Bronchopleural fistula (BPF) after lung cancer surgery is a life-threatening complication and often needs two-stage closure after fenestration. Although one-stage closure of BPF is challenging, it would provide shorter treatment time and lower patient physical burden than two-stage closure. However, there have been few reports of one-stage closure of a large BPF. PRESENTATION OF CASE: A 53-year-old man underwent robotic right lower lobectomy with systematic lymph node dissection. Postoperative bronchoscopy revealed an ischemic change in the bronchial stump, which progressed to a large BPF. However, under the preemptive antibiotic treatment without chest drainage, local infection was controlled within a limited pleural space. We successfully performed one-stage closure of a 3-cm sized BPF with pedicled latissimus dorsi (PLD) muscle flap. DISCUSSION: Early diagnosis of ischemic bronchitis and appropriate preceding antibiotic treatment could minimize the local infection around the fistula. To our knowledge, our case represented the largest BPF that was successfully treated by one-stage procedure using preemptive antibiotics and the PLD muscle flap. CONCLUSION: One-stage closure using the PLD muscle flap may be a treatment option even for a 3-cm sized BPF, wherein infection is controlled and the relevant pleural cavity is limited.

Programmed death-ligand 1 expression profiling in thymic epithelial cell tumors: Clinicopathological features and quantitative digital image analyses.

OBJECTIVES: Whether the extent of expression of programmed death-ligand 1 (PD-L1) is clinically significant remains uncertain, although immuno-oncological features have been studied in thymic epithelial cell tumors (TETs). We investigated the histological features of PD-L1 expression in TETs, and assessed PD-L1 expression using digital image analysis. MATERIALS AND METHODS: Participants comprised 66 patients with TET who underwent surgical resection between 2001 and 2016. We calculated tumor cell-positive ratio as total proportion score (TPS) with immunohistochemistry using SP263 anti-PD-L1 monoclonal antibody. PD-L1 expression was also quantified using digital image analysis of whole-slide images. We evaluated the relationship between conventional visual TPS using optical microscopy (TPS-V) and TPS from digital image analysis (TPS-IA). We further classified all TETs into high or low PD-L1 expression groups and assessed the clinical significance of PD-L1 expression level using TPS-V and TPS-IA. RESULTS: WHO histological types were Type A (n = 8), AB (n = 18), B1 (n = 5), B2 (n = 16), B3 (n = 6), metaplastic thymoma (n = 2), and thymic carcinoma (TC) (n = 11). Median TPS-Vs were 2%, 2%, 10 %, 65 %, 90 %, 1%, and 20 %, respectively. TPS-IAs correlated with TPS-Vs in TETs overall and in thymomas, but not in TCs. PD-L1 expression levels in TETs differed significantly among histological types. Whether TPS-V or TPS-IA were used, the PD-L1high group included more cases of the more aggressive histological types. Recurrence-free survival (RFS) was shorter in the PD-L1high group than in the PD-L1low group in thymoma using TPS-IA, whereas RFS of the PD-L1high group was shorter in all TETs using TPS-V. CONCLUSION: PD-L1 expression levels depended on the histological type of TET. Extensive PD-L1 expression in TETs was associated with poor prognosis. Digital image analysis is feasible for evaluating PD-L1 expression in TETs and might offer clinically relevant features of thymomas.