Late cardiac tamponade after a helix-based active fixation leadless pacemaker implantation.

Although the late cardiac tamponade in leadless pacemaker implantation (LPI) is rare, we encountered such an incident in patient with AVEIR-VR™ system on hemodialysis and warfarinization. When LPI with active fixation system, we should aim for successful single-attempt deployment using electrical premapping to prevent cardiac tamponade including the late phase.

Successful direct pacing of the left bundle branch area with ICD lead using steerable delivery sheath.

Recently, conduction system pacing has been performed in patients with impaired cardiac function. We report a case in which a DF4 implantable cardioverter defibrillator lead was screwed directly into the left bundle branch area with the support of a steerable delivery sheath.

Chronic phase subcutaneous implantable cardioverter defibrillator lead dislodgement in a patient with arrhythmogenic right ventricular cardiomyopathy.

The subcutaneous implantable cardioverter defibrillator (S-ICD) is often used in young patients such as arrhythmogenic right ventricular cardiomyopathy (ARVC) and Brugada syndrome due to long-term lead durability issues. Although S-ICD lead dislodgement is rare, we encountered such an incident in a young ARVC patient during the chronic phase following the two-incision technique. Remote monitoring system is useful for early diagnosis of electrode movement (Graphical abstract image). When S-ICD lead dislodgement occurs in active young patients, lead revision using the three-incision technique may be an option.

Combined effects of high atrial septal pacing and reactive atrial antitachycardia pacing for reducing atrial fibrillation in sick sinus syndrome.

Background: It is unknown whether atrial fibrillation (AF) burden varies by pacing site in patients with reactive atrial antitachycardia pacing (rATP). We aimed to compare AF burden in patients with high atrial septal pacing (HASp) via delivery catheter and right atrial appendage pacing (RAAp) in patients with sick sinus syndrome (SSS). Methods: We retrospectively identified 109 patients with a history of paroxysmal AF and SSS who had received dual-chamber pacemaker implantation between January 2017 and December 2019, of whom 39 and 70 patients had HASp and RAAp, respectively. rATP was initiated after a 1-month post-implantation run-in period. Results: Patients with HASp had a significantly shorter P-wave duration during atrial pacing than those with RAAp (99.3 ± 10.4 vs. 116.0 ± 14.3 ms, p < .001). During the 3-year follow-up period, the incidence of an AF lasting longer than 1 or 7 days was significantly lower (hazard ratio [HR], 0.45; p = .016; HR, 0.24; p = .004) than in those with RAAp. The median time of AF/AT per day in the follow-up periods was significantly shorter in the HASp group than in the RAAp group (10 vs. 18 min/day, p = .018). Atrial lead division did not occur in the HASp group during the follow-up period. Conclusions: HASp via delivery catheter is as safe as RAAp, and HASp combined with rATP is effective for reducing AF burden in patients with SSS and paroxysmal AF.

Modified Clagett procedure for acute pleural empyema.

Pleural empyema often requires surgical intervention; however, surgical invasiveness should be minimized. We utilized the modified Claget procedure as an alternative to thoracoplasty for acute pleural empyema with a dead space. The procedure was performed as follows: first, 500 mg of kanamycin and 500,000 units of polymyxin sulfate dissolved in 10-100 ml saline was instilled intrapleurally via tube thoracostomy. The chest tube was clamped overnight and then removed. The modified Clagett procedure might be effective for acute pleural empyema with a dead space without pulmonary or bronchopleural fistula. We report our successful experience of performing modified Clagett procedure for pleural empyema with a dead space, through a detailed case presentation.

PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes.

PD-1 blockade exerts clinical efficacy against various types of cancer by reinvigorating T cells that directly attack tumor cells (tumor-specific T cells) in the tumor microenvironment (TME), and tumor-infiltrating lymphocytes (TILs) also comprise nonspecific bystander T cells. Here, using single-cell sequencing, we show that TILs include skewed T cell clonotypes, which are characterized by exhaustion (Tex) or nonexhaustion signatures (Tnon-ex). Among skewed clonotypes, those in the Tex, but not those in the Tnon-ex, cluster respond to autologous tumor cell lines. After PD-1 blockade, non-preexisting tumor-specific clonotypes in the Tex cluster appear in the TME. Tumor-draining lymph nodes (TDLNs) without metastasis harbor a considerable number of such clonotypes, whereas these clonotypes are rarely detected in peripheral blood. We propose that tumor-infiltrating skewed T cell clonotypes with an exhausted phenotype directly attack tumor cells and that PD-1 blockade can promote infiltration of such Tex clonotypes, mainly from TDLNs.

Surgical outcome of pulmonary artery reconstruction using the expanded polytetrafluoroethylene patch in patients with lung cancer.

PURPOSE: Pulmonary artery reconstruction is sometimes utilized as an alternative to pneumonectomy in lung cancer surgery. We herein report our experience of pulmonary artery reconstruction using an expanded polytetrafluoroethylene (ePTFE) patch based on the surgical results and long-term outcome. METHODS: Clinical records of lung cancer patients who underwent patch plasty were reviewed retrospectively. RESULTS: Between 2003 and 2017, pulmonary artery patch plasty were performed in 21 patients [18 males, 3 females; mean age 65 (range 47-79) years]. Induction chemoradiotherapy was performed in three patients. Bronchoplasty was performed in five patients. The pathologic stages were stage I in 3 patients, stage II in 6 and stage III in 12. Pneumonectomy, lobectomy and segmentectomy were performed in 2, 18 and 1 patient, respectively. The left upper lobe was the most frequent origin of lung cancer (15 patients). There was no reconstruction-related morbidity or mortality. The overall survival rate at 5 years was 64.1% with a mean follow-up of 39.5 months, and the survival rates for N0-1 and N2-3 were 80.8% and 28.6%, respectively. CONCLUSION: Patch angioplasty using the ePTFE sheet is a reliable procedure in radical surgery for lung cancer.

Evaluating vertebral artery dominancy before T4 lung cancer surgery requiring subclavian artery reconstruction.

PURPOSES: To evaluate vertebral artery (VA) dominancy and the risk of brain infarction in T4 lung cancer patients with tumor invasion into the subclavian artery. METHODS: We reconstructed the subclavian artery in 10 patients with T4 non-small cell lung cancer. The histological stages were IIIA in eight patients and IIIB in two patients. We evaluated the VA dominancy by performing a four-vessel study preoperatively and investigated the relationship between the methods of VA treatment and postoperative brain complications, retrospectively. RESULTS: Seven patients had a superior sulcus tumor (SST) and three had direct invasion into the mediastinum. Based on the tumor location, a transmanublial approach was used in five patients and a posterolateral hook incision was used in the other five. All subclavian artery (SA) reconstructions were done using an artificial woven graft. Preoperative angiography of the VA revealed poor development of the contralateral side in two patients. One of these patients suffered a severe brain infarction on postoperative day 2, which proved fatal. In the other patient, the VA was connected to the left SA graft by a side-to-end anastomosis and there was no postoperative brain complication. CONCLUSIONS: Preoperative SA and VA angiography is mandatory for identifying the need for VA reconstruction in lung cancer patients with major arterial invasion.

Relationship between n-3 Polyunsaturated Fatty Acids and Extent of Vessel Disease in Patients with ST Elevation Myocardial Infarction.

A relationship between serum polyunsaturated fatty acids (PUFAs) and cardiovascular disease has been reported; however, the existence of a relationship between serum PUFAs and extent of vessel disease (VD) in patients with ST elevation myocardial infarction (STEMI) remains unclear.Between July 2011 and June 2015, 866 consecutive STEMI patients underwent emergent percutaneous coronary intervention, 507 of whom were enrolled and classified into three groups according to the initial angiograms: 1VD, 294 patients; 2VD, 110 patients; and 3VD/left main trunk disease (LMTD), 103 patients. Serum levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid, and other laboratory data during hospitalization were evaluated.The serum EPA level in the 3VD/LMTD group was significantly lower than that in the 1VD group (55.5 ± 22.1 versus 66.2 ± 28.7, P = 0.002) and was slightly lower than that in the 2VD group (55.5 ± 22.1 versus 65.2 ± 28.9, P = 0.0167). Multivariate adjustment analysis revealed that age ≥ 70 years (odds ratio, 1.72; 95% confidence interval, 1.03-2.89; P = 0.038) and a low serum EPA level (odds ratio, 0.98; 95% confidence interval, 0.99-1.00; P = 0.023) were independent risk factors for 3VD/LMTD, while a low serum DHA level was not.A low serum EPA level may be more strongly related than a low serum DHA level to the extent of VD in STEMI patients. Age ≥ 70 years and a low serum EPA level may be independent risk factors for 3VD/LMTD.

Randomized controlled phase III trial of adjuvant chemo-immunotherapy with activated killer T cells and dendritic cells in patients with resected primary lung cancer.

PURPOSE: We conducted a phase III randomized controlled trial (RCT) to investigate the efficacy of postsurgical adjuvant immunotherapy combined with chemotherapy. The immunotherapy targets were residual micrometastases and clones resistant to chemotherapy. PATIENTS AND METHODS: Between April 2007 and July 2012, 103 postsurgical non-small cell lung cancer patients were randomly assigned to receive either chemo-immunotherapy (group A) or chemotherapy (group B). The immunotherapy consisted of the adoptive transfer of autologous activated killer T cells and dendritic cells obtained from the lung cancer patients' own regional lymph nodes. RESULTS: The 2-year overall survival rates in groups A and B were 93.4 and 66.0 %, and the 5-year rates were 81.4 and 48.3 %, respectively. The differences were statistically significantly better in group A. The hazard ratio (HR) was 0.229 (p = 0.0013). The 2- and 5-year recurrence-free survival rates were 68.5, 41.4 and 56.8, 26.2 % in groups A and B, respectively. Those differences were also statistically significant (log-rank test p = 0.0020). The HR was 0.423 (p = 0.0027) in favor of group A. As for adverse reactions to immunotherapy, of a total of 762 courses, 52 (6.8 %) were accompanied with chills and shivering, and 47 (6.2 %), with fever (>38 °C). CONCLUSIONS: Immunotherapy has the potential to improve the postsurgical prognosis of lung cancer patients, but a large-scale multi-institutional RCT is awaited for further confirmation of this study.

Pituitary apoplexy after surgical treatment of lung cancer.

Pituitary apoplexy is a rare but potentially life-threatening condition caused by the sudden enlargement of a pituitary adenoma secondary to infarction and hemorrhage. Surgical stress is 1 cause of pituitary apoplexy, but asymptomatic pituitary adenomas are difficult to diagnose preoperatively. Here we report a case of a 78-year-old male who had postoperative pituitary apoplexy after surgery for lung cancer. He underwent right upper and middle lobectomy and lymph node dissection for squamous cell carcinoma with obstructive pneumonia. On the sixth postoperative day he developed sudden-onset fever, respiratory distress, and polyuria. Brain magnetic resonance imaging revealed an enlarged, hemorrhagic pituitary gland. He was treated with steroid hormone replacement. Subsequent endocrine hormone stress tests revealed recovery of his pituitary function. Based on his clinical course, the patient was diagnosed with acute adrenal insufficiency and diabetes insipidus due to pituitary apoplexy.

Endobronchial ultrasonography for positron emission tomography and computed tomography-negative lymph node staging in non-small cell lung cancer.

BACKGROUND: Integrated positron emission tomography (PET) with computed tomography (CT) is a useful modality to investigate lymph node metastases for non-small cell lung cancer, but is less sensitive for normal-sized lymph nodes. We sometimes encounter cases with radiologically normal lymph nodes and unsuspected mediastinal metastases detected by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). However, few studies have investigated staging in patients with radiologically normal mediastina, and the accuracy of EBUS-TBNA staging for radiologically normal mediastina and hila is unclear. METHODS: This study was a retrospective, single-institution review of a prospectively maintained database at Chiba Cancer Center between May 1, 2008, and September 1, 2013. We analyzed 113 non-small cell lung cancer patients with both CT-negative and PET/CT-negative lymph nodes (N0) in preoperative nodal staging performed by EBUS-TBNA. After preoperative staging was performed, patients with either N0 or N1 clinical staging underwent surgery. Final N factors were determined by mediastinal lymphadenectomy. RESULTS: In our study, the overall rate of N2 disease was 17.6% (20 of 113). For nodal staging by EBUS-TBNA, the sensitivity, specificity, negative predictive value, and diagnostic accuracy were 35.0% (7 of 20), 100% (93 of 93), 87.7% (93 of 106), and 88.4% (100 of 113), respectively. There were no severe complications from EBUS-TBNA staging. CONCLUSIONS: The overall rate of unsuspected N2 was not low. EBUS-TBNA was accurate and feasible for preoperative mediastinal nodal staging of non-small cell lung cancer with both CT-negative and PET/CT-negative lymph nodes. The sensitivity of EBUS-TBNA for radiologically normal mediastina and hila was low. Further investigations are required.

The impact of combined pulmonary fibrosis and chronic obstructive pulmonary disease on long-term survival after lung cancer surgery.

PURPOSE: The purpose of this study was to determine the impact of pulmonary fibrosis (PF) on postoperative complications and on long-term survival after surgical resection in lung cancer patients with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: A retrospective chart review was conducted of 380 patients with COPD who had undergone pulmonary resection for lung cancer at the University Hospital between 1990 and 2005. The definition of COPD was a preoperative forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of less than 70%; PF was defined as obvious bilateral fibrous change in the lower lung fields, confirmed by computed tomography. RESULTS: PF was present in 41 patients (10.8%) with COPD; the remaining 339 patients (89.2%) did not have PF. The preoperative FVC/FEV1 was significantly lower in the group of patients with PF than in the group without (p < 0.05). Acute lung injury and home oxygen therapy were significantly more common in the PF group; however, the 30-day mortality was similar between the groups. The cumulative survival at 3 and 5 years was 53.6 and 36.9%, respectively, in the PF group and 71.4 and 66.1%, respectively, in the non-PF group (p = 0.0009). Increased age, decreased body mass index, advanced pathologic stage, and the existence of PF were identified as independent risk factors for decreased survival. CONCLUSION: PF is a risk factor for decreased survival after surgical treatment in lung cancer patients with COPD.

Pericardial synovial sarcoma: a case report and review of the literature.

Primary pericardial synovial sarcoma is a rare disease. We herein report a case of synovial sarcoma that originated in the epicardium. A 13-year-old male visited our hospital with a fever and chest pain. Copious pericardial effusion and a large intrapericardial tumor were detected. An open-chest tumor resection was performed. A solid nodular tumor was observed in the pericardial cavity. The tumor was a polypoid mass that was pedunculated and grew from the inner surface of the pericardium near the origin of the SVC and ascending aorta. Histologically, the tumor cells were uniformly spindle shaped, with an ovoid or oval nucleus, and formed solid, compact sheets and fascicles. A storiform pattern was also observed. Based on the histopathological and immunohistochemical findings, and the fluorescence in situ hybridization detection of rearrangement of the SYT gene, a monophasic synovial sarcoma was diagnosed. We discuss the diagnosis and treatment of this case and review the pertinent literature.

Optical coherence tomography findings in lesions after sirolimus-eluting stent implantation with peri-stent contrast staining.

BACKGROUND: We have sometimes noted abnormal angiographic coronary dilatation, <50% of the reference vessel, at the site of sirolimus-eluting stent implantation, suggesting contrast staining outside the stent struts and named this finding peri-stent contrast staining (PSS). Little was known about optical coherence tomography findings of lesions with PSS. METHODS AND RESULTS: Between May 2008 and March 2010, we performed optical coherence tomography for 90 in-stent restenosis lesions after sirolimus-eluting stent implantation. We found PSS in 20 of the 90 lesions by coronary angiography. The differences in optical coherence tomography findings, including incomplete stent apposition, multiple interstrut hollows (MIH), strut coverage, and thrombus, were compared between lesions with PSS and those without PSS. PSS is defined as contrast staining outside the stent contour extending to >20% of the stent diameter measured by quantitative coronary angiography. MIH is defined as multiple hollows (the maximum depth >0.5 mm) existing between and outside well-apposed stent struts. Both incomplete stent apposition (60.0% versus 10%; P<0.001) and MIH (85.0% versus 25.7%; P<0.001) were frequently observed in lesions with PSS than in lesions without PSS. Among the 20 lesions with PSS, there was only 1 lesion in which we found neither MIH nor incomplete stent apposition, but only minor dissection. Uncovered struts (11.6% versus 3.9%; P=0.001), malapposed struts (2.0% versus 0.0%; P<0.001), and red thrombus (35% versus 10%; P=0.012) were frequently observed in lesions with PSS than in lesions without PSS. CONCLUSIONS: PSS might be closely associated with 2 different optical coherence tomography findings, MIH and incomplete stent apposition, in lesions after sirolimus-eluting stent implantation.

ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity.

BACKGROUND: Anaplastic lymphoma kinase (ALK) fusion gene-positive lung cancer accounts for 4-5% of non-small cell lung carcinoma. A clinical trial of the specific inhibitor of ALK fusion-type tyrosine kinase is currently under way. METHODS: ALK fusion gene products were analyzed immunohistochemically with the materials obtained by surgery or by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The echinoderm microtubule-associated protein-like 4(EML4)-ALK or kinesin family member 5B (KIF5B)-ALK translocation was confirmed by the reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). After eligibility criteria were met and informed consent was obtained, 3 patients were enrolled for the Pfizer Study of Crizotinib (PF02341066), Clinical Trial A8081001, conducted at Seoul National University. RESULTS: Out of 404 cases, there were 14 of EML4-ALK non-small cell carcinoma (NSCLC) and one KIF5B-ALK NSCLC case (8 men, 7 women; mean age, 61.9 years, range 48-82). Except for 2 light smokers, all patients were non-smokers. All cases were of adenocarcinoma with papillary or acinar subtypes. Three were of stage IA, 5 of stage IIIA, 1 of stage IIIB and 6 of stage IV. Ten patients underwent thoracotomy, 3 received chemotherapy and 2 only best supportive care (BSC). One BSC and 2 chemotherapy cases were enrolled for the clinical trial. Patients with advanced stages who received chemotherapy or best supportive care were younger (54.0±6.3) than those who were surgically treated (65.8±10.1) (p<0.05). The powerful effect of ALK inhibitor on EML4-ALK NSCLC was observed. Soon after its administration, almost all the multiple bone and lymph node metastases quickly disappeared. Nausea, diarrhea and the persistence of a light image were the main side effects, but they diminished within a few months. CONCLUSION: ALK-fusion gene was found in 3.7% (15/404) NSCLC cases and advanced disease with this fusion gene was correlated with younger generation. The ALK inhibitor presented in this study is effective in EML4-ALK NSCLC cases. A further study will be necessary to evaluate the clinical effectiveness of this drug.

Effectiveness of paclitaxel-eluting balloon catheter in patients with sirolimus-eluting stent restenosis.

OBJECTIVES: The aim of this study was to investigate the efficacy of a paclitaxel-eluting balloon (PEB) for the treatment of sirolimus-eluting stent (SES) restenosis. BACKGROUND: Because drug-eluting stents (DES) are being used in increasingly complicated settings, DES restenosis is no longer an uncommon phenomenon, and its optimal treatment is unknown. METHODS: This study was a prospective single-blind randomized trial conducted in 50 patients with SES restenosis. Patients were randomly assigned to a PEB group (n = 25) or a conventional balloon angioplasty (BA) group (n = 25). The primary end point was late lumen loss at 6-month follow-up. Secondary end points included the rate of binary restenosis (in-segment analysis) and major adverse cardiac events (MACE) at 6-month follow-up. RESULTS: At 6-month angiographic follow-up (follow-up rate: 94%), in-segment late lumen loss was lower in the PEB group than in the BA group (0.18 ± 0.45 mm vs. 0.72 ± 0.55 mm; p = 0.001). The incidence of recurrent restenosis (8.7% vs. 62.5%; p = 0.0001) and target lesion revascularization (4.3% vs. 41.7%; p = 0.003) was also lower in the PEB group than in the BA group. The cumulative MACE-free survival was significantly better in the PEB group than in the BA group (96% vs. 60%; p = 0.005). CONCLUSIONS: In patients with SES restenosis, PEB provided much better clinical, angiographic outcomes than conventional BA.

Molecular characterization of chronic obstructive pulmonary disease-related non-small cell lung cancer through aberrant methylation and alterations of EGFR signaling.

BACKGROUND: The aim of this study was to evaluate the molecular influence of chronic obstructive pulmonary diseases (COPD) on the pathogenesis of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The methylation profiles of 12 genes, and the epidermal growth factor receptor (EGFR) and KRAS mutations were determined for samples from 229 NSCLC patients. In addition, protein expression of EGFR and HER2 in 116 NSCLCs was analyzed based on the presence or absence of COPD. RESULTS: IL-12Rbeta2 and Wif-1 methylation and HER2 overexpression were more frequent events in the COPD group. Eighty nonmalignant lung tissues had no correlation with any molecular changes between the COPD and the non-COPD group. EGFR mutation was significantly higher in the non-COPD group, while EGFR expression was inversely correlated with %FEV1.0. In the COPD group, unmethylated SPARC and sFRP-2 genes or a negative CpG island methylator phenotype (CIMP) was a negative prognostic factor, while methylation of p16(INK4A) and WNT antagonist genes was a negative prognostic factor in the non-COPD group. CONCLUSIONS: Novel characteristics of COPD-related NSCLC were identified by examination of methylation profiles and alterations of EGFR signaling. In consideration of the high sensitivity to smoking in patients with COPD, NSCLC with COPD might be a distinct population of smoke-related NSCLC, the genetic profile of which is quite different from non-COPD NSCLC.

Promoter hypermethylation of the p16 and Wif-1 genes as an independent prognostic marker in stage IA non-small cell lung cancers.

Hypermethylation of promoter CpG islands is a major inactivation mechanism of tumor suppressor genes, some of which are thought to be related to the prognosis of patients with non-small cell lung cancer (NSCLC). Therefore, hypermethylation of the specific genes may be expected to serve as a prognostic biomarker for NSCLC. In this study, the methylation status of 14 genes was analyzed in 44 stage IA NSCLC cases using methylation-specific PCR. Hypermethylation was detected in PTGER2 (70% of cases), DRM/Gremlin (66%), sFRP-2 (57%), IL-12Rbeta2 (48%), Reprimo (41%), APC (39%), CXCL12 (39%), HPP1 (30%), SPARC (30%), sFRP-5 (30%), p16 (25%), RUNX3 (20%), sFRP-1 (20%) and Wif-1 (16%). Patients with p16, sFRP-5, Wif-1 or CXCL12 methylation had a significantly shorter duration of relapse-free survival than their counterparts with an unmethylated gene (p16, P=0.011; sFRP-5, P=0.030, Wif-1, P=0.036; CXCL12, P=0.026). Also, those with methylated HPP1, p16 or Wif-1 had a significantly shorter duration of overall survival (HPP1, P=0.031; p16, P=0.026; Wif-1, P=0.008). Multivariate analysis revealed that p16 methylation in relapse-free survival and Wif-1 methylation in overall survival were the strongest independent prognostic factors (p16, P=0.036; Wif-1, P=0.035). In conclusion, the hypermethylation of the p16 and Wif-1 genes has potential as biomarkers that may be used to predict the prognosis of stage IA NSCLC.