Optimal timing for local ablative treatment of bone oligometastases in non-small cell lung cancer.

Oligometastases is a term commonly used to describe a disease state characterized by a limited number of distant metastases, and represents a transient phase between localized and widespread systemic diseases. This subgroup of stage IV cancer has increased in clinical importance due to the possibility of curative rather than palliative treatment. Among advanced lung cancer patients, 30-40% show bone metastases, and can show complications such as pathological fractures. Many prospective studies have shown efficacy of localized treatment in oligometastatic non-small cell lung cancer (NSCLC) in improving progression-free survival and overall survival. Compared to metastases in other organs, bone metastases are unique in terms of tumor microenvironment and clinical outcomes. Radiotherapy is the most frequently used treatment modality for local ablative treatment for both primary and metastatic lesions. Stereotactic body radiation therapy demonstrated more rapid and effective pain control compared to conventional 3D conformal radiotherapy. Radiotherapy improved outcomes in terms of time-to-skeletal related events skeletal-related events (SRE), hospitalization for SRE, pain relief, and overall survival in patients with bone metastases. Decision on timing of local ablative treatment depends on patient's overall clinical status, treatment goals, potential side effects of each approach, and expected initial responses to systemic anti-cancer treatment.

Prognostic Implication of Exfoliative Airway Pathology in Cancer-Free Coal Workers' Pneumoconiosis.

BACKGROUND: The purpose of this study is to see if exfoliative pulmonary airway pathology in cancer-free coal workers' pneumoconiosis (CWP) can be used as a biomarker for predicting pulmonary morbidity. METHODS: We investigated persistent metaplastic changes in bronchoscopic washing cytology and differential cell counts in bronchoalveolar lavages (BAL) in 97 miners with CWP and 80 miners without CWP as the control. Clinicopathological parameters were examined including pulmonary function tests and the presence of progressive massive fibrosis. RESULTS: When compared to the control group, severe alveolitis, severe goblet cell hyperplasia (GCH), severe hyperplastic epithelial change, and severe squamous metaplasia were the distinguishing biomarkers in CWP. Multivariate analysis revealed that severe alveolitis and severe GCH, along with miner duration and current smoker, were independent predictors of pulmonary mortality. The survival analysis revealed a significantly different survival rate between the three groups: no evidence of severe alveolitis and severe GCH, presence of severe alveolitis or severe GCH but not both, and both severe alveolitis and severe GCH. CONCLUSIONS: The severities of alveolitis and goblet cell hyperplasia in the bronchoscopic study are independent prognostic factors for CWP. A pathologic grading system based on these two parameters could be used in the stratification and clinical management of CWP patients.

Comprehensive Comparison of 22C3 and SP263 PD-L1 Expression in Non-Small-Cell Lung Cancer Using Routine Clinical and Conditioned Archives.

PD-L1 harmonization studies revealed a strong correlation between the 22C3 and SP263 assays in non-small-cell lung cancer (NSCLC). However, the assays' characteristics have yet to be validated in a variety of clinical and analytical settings. The results of 431 NSCLC samples tested concurrently in routine clinical practice with the PD-L1 22C3 and SP263 assays were reviewed, and both assays were performed on 314 archives of surgically resected NSCLCs to assess PD-L1 expression in relation to variables such as FFPE block age and FFPE section storage condition. In routine clinical samples, 22C3 showed the highest concordance rate with 94.5% of SP263 tumor proportion score (TPS) ≥50% and 92.3% of SP263 TPS ≥1%, while SP263 showed a concordance rate with 79.6% of 22C3 TPS ≥50% and 89.9% of 22C3 TPS ≥1%. In the archival analysis, the high TPS of 22C3 and SP263 (versus TPS 1%) were significantly associated with a more recent block (<3 years versus ≥3 years) (p = 0.007 and p = 0.009, respectively). Only the TPS of 22C3 was reduced when FFPE sections were stored at room temperature compared to SP263. However, when stored at 4 °C, the storage duration had no effect on expression in either assay. For 22C3 TPS 1−49 percent and ≥50 percent (OR = 1.73, p = 0.006 and OR = 1.98, p = 0.002, respectively). There was a considerably larger chance of preserved 22C3 expression in recent room-temperature paraffin section storage, although SP263 demonstrated preserved expression in prolonged room-temperature section storage. Despite the good association between PD-L1 22C3 and SP263 in routine clinical samples, FFPE blocks older than 3 years and sections held at room temperature for more than 1 week may result in an underestimation of PD-L1 status, particularly for the 22C3 test. However, the SP263 assay was more sensitive under these conditions.

Atypical Thymic Carcinoid in a Patient with Zollinger-Ellison Syndrome.

Atypical thymic carcinoid is an extremely rare tumor with a poor prognosis. In addition to its known association with multiple endocrine neoplasia type 1, its hallmark characteristics include local invasion and early distant metastasis. In this report, we share our experience treating atypical thymic carcinoid in a patient with Zollinger-Ellison syndrome.

PD-L1 expression in ROS1-rearranged non-small cell lung cancer: A study using simultaneous genotypic screening of EGFR, ALK, and ROS1.

BACKGROUND: The aim of the current study was to investigate the prevalence and clinicopathologic characteristics of ROS1-rearranged non-small cell lung cancer (NSCLC) in routine genotypic screening in conjunction with the study of PD-L1 expression, a biomarker for first-line treatment decisions. METHODS: Reflex simultaneous genotypic screening for EGFR by peptide nucleic acid clamping, and ALK and ROS1 by fluorescence in situ hybridization (FISH) was performed on consecutive NSCLC cases at the time of initial pathologic diagnosis. We evaluated genetic aberrations, clinicopathologic characteristics, and PD-L1 tumor proportion score (TPS) using a PD-L1 22C3 assay kit. RESULTS: In 407 consecutive NSCLC patients, simultaneous genotyping identified 14 (3.4%) ROS1 and 19 (4.7%) ALK rearrangements, as well as 106 (26%) EGFR mutations. These mutations were mutually exclusive and were found in patients with similar clinical features, including younger age, a prevalence in women, adenocarcinoma, and advanced stage. The PD-L1 assay was performed on 130 consecutive NSCLC samples. High PD-L1 expression (TPS ≥ 50%) was observed in 29 (22.3%) tumors. PD-L1 expression (TPS ≥ 1%) was significantly associated with wild type EGFR, while ROS1 rearrangement was associated with high PD-L1 expression. Of the 14 cases with ROS1 rearrangement, 12 (85.7%) showed PD-L1 expression and 5 (35.7%) showed high PD-L1 expression. CONCLUSION: In the largest consecutive routine Asian NSCLC cohort analyzed to date, we found that high PD-L1 expression frequently overlapped with ROS1 rearrangement, while it negatively correlated with EGFR mutations.

A clinical decision-making model for repeat surgical treatment of pectus Bar displacement: distance measurement after nuss procedure.

BACKGROUND: Bar displacement is one of the most common and serious complications after the Nuss procedure. However, measurements of and factors affecting bar displacement have not been reported. The objectives of this study were to develop a decision model to guide surgeons considering repeat treatment and to estimate optimal cut-off values to determine whether reoperation to correct bar displacement is warranted. METHODS: From July 2011 to August 2013, ninety bars were inserted in 61 patients who underwent Nuss procedures for pectus excavatum. Group A did not need surgical intervention and Group B required reoperation for bar displacement. Bar position was measured as the distance from the posterior superior end of the sternal body to the upper border of the metal bar on lateral chest radiographs. The bar displacement index (BDI) was calculated using D0 - Dx / D0 x 100 (D0: bar position the day after surgery; Dx: minimal or maximal distance of bar position on the following postoperative days). The optimal cut-off values of BDI warranting reoperation were assessed on the basis of ROC curve analysis. RESULTS: Of the 61 patients, 32 had single bars inserted whereas 29 had parallel bars inserted. There was a significant difference in age (14.0 ± 7.5 vs. 23.3 ± 12.0, p = 0.0062), preoperative Haller index (HI) (4.0 ± 1.1 vs. 5.0 ± 1.0, p = 0.033), and postoperative HI (2.7 ± 0.4 vs. 3.2 ± 0.5 p = 0.006) between the two groups. The optimal cut-off value of BDI was 8.7. CONCLUSIONS: We developed a BDI model for surgeons considering performing reoperation after Nuss procedure. The optimal cut-off value of BDI was 8.7. This model may help surgeons to decide objectively whether corrective surgery should be performed. The main factors affecting the relationship between bar displacement and reoperation were age and preoperative HI.

A new protocol for concomitant needle aspiration biopsy and localization of solitary pulmonary nodules.

BACKGROUND: Pulmonary nodules may require thoracoscopic resection in cases where percutaneous needle aspiration (PCNA) is non-diagnostic or not technically feasible. We developed a new protocol to localize pulmonary nodules concomitantly with PCNA. We retrospectively reviewed the use of concomitant PCNA and preoperative localization under computed tomography (CT) guidance. METHODS: From Jan 2006 to Dec 2013, we performed PCNA and localization concomitantly on 34 pulmonary nodules (in 33 patients) using self-made, platinum microcoils. Patients in which PCNA results were less likely to be non-diagnostic and who were anticipating thoracoscopy were eligible to participate in this study. The CT-guided PCNA biopsy and microcoil localization was performed on the day of the VATS in the CT suite. The PCNA specimen was sent to the pathologist for frozen section pathology. If diagnosis of the lesion was not confirmed by PCNA or was primary lung cancer, the patient was moved to the operating room for VATS surgery. RESULTS: Between Jan 2006 and Dec 2013, concomitant PCNA and localization were successfully performed on 34 pulmonary nodules from 33 patients (one patient had two nodules). Of the 34 nodules, seven were diagnosed pathologically using PCNA, and 27 nodules that could not be diagnosed by PCNA were excised by thoracoscopic resection without additional procedures or time because of concomitant localization. There were no deaths or significant morbidities. Minor complications included three incidents of lung hemorrhage and five of pneumothorax (two required closed thoracostomy drainage). Of 34 nodules in which both PCNA and localization were used, thoracoscopic resections were performed on 33, lobectomies were performed concomitantly with thoracoscopic resection on 11. Intraoperative fluoroscopy was used to detect 33 of 34 nodules localized using the platinum microcoil (97.06 %) or to guide stapling during thoracoscopic resection. CONCLUSIONS: The advantages of this technique are 1) there is no need for further localization during thoracoscopy even in cases of unsuccessful PCNA, 2) it is more effective with respect to both cost and time, and 3) it provides greater patient comfort.

Recurrent intractable hiccups treated by cervical phrenic nerve block under electromyography: report of a case.

Intractable or persistent hiccups require intensive or invasive treatments. The use of a phrenic nerve block or destructive treatment for intractable hiccups has been reported to be a useful and discrete method that might be valuable to patients with this distressing problem and for whom diverse management efforts have failed. We herein report a successful treatment using a removable and adjustable ligature for the phrenic nerve in a patient with recurrent and intractable hiccups, which was employed under the guidance of electromyography.

Late-developing tongue adenoid cystic carcinoma after pulmonary metastasectomy: a case report.

Adenoid cystic carcinoma (ACC) is a relatively rare epithelial tumor of the salivary glands that accounts for approximately 5 to 10% of all salivary gland neoplasms. The typical clinical and pathological findings of this tumor include slow indolent growth, common local recurrence, and late distant metastasis to lung, brain, bone, liver, thyroid, and spleen. We report a 52-year-old female patient who presented a tongue ACC, 27 months after successful pulmonary ACC resection.

Intractable hiccup accompanying pleural effusion: reversible clipping of an intrathoracic phrenic nerve.

Hiccup is usually a self-limiting condition, and can be treated with medications and physical maneuvers. However, hiccup episodes continuing for days or weeks can be incapacitating, and disturb work, sleep, and eating. Therefore, timely therapeutic intervention is needed to achieve early resolution of this treatable condition. We report on a successful phrenic nerve block for intractable hiccups, which consisted of thoracoscopic nerve clipping under general anesthesia and reversal under local anesthesia. This method has the advantage of assured diaphragmatic functional recovery while controlling intractable hiccups.

Cholesterol granuloma: a rare benign rib tumor.

Rib tumors are uncommon, constituting only 5% to 10% of all bony neoplasms. Cholesterol granuloma is also rare and is described as inflammatory granulation that occurs in response to the deposition of cholesterol crystals. Cholesterol granulomas are found most commonly in the paranasal sinuses or temporal bones, but there are also rare reports of their occurrence in the peritoneum, parotid gland, lymph nodes, thyroglossal duct, kidney, liver, and spleen. Involvement of the ribs has rarely been described previously. We report a rare case of cholesterol granuloma involving the second rib of a 38-year-old-woman who presented with a slowly growing lesion of the anterior aspect of the chest.

Recurrent cervical esophageal stenosis after colon conduit failure: use of myocutaneous flap.

A 53-year-old male developed cervical esophageal stenosis after esophageal bypass surgery using a right colon conduit. The esophageal bypass surgery was performed to treat multiple esophageal strictures resulting from corrosive ingestion three years prior to presentation. Although the patient underwent several endoscopic stricture dilatations after surgery, he continued to suffer from recurrent esophageal stenosis. We planned cervical patch esophagoplasty with a pedicled skin flap of sternocleidomastoid (SCM) muscle. Postoperative recovery was successful, and the patient could eat a solid meal without difficulty and has been well for 18 mo. SCM flap esophagoplasty is an easier and safer method of managing complicated and recurrent cervical esophageal strictures than other operations.

Occlusive vascular Ehlers-Danlos syndrome accompanying a congenital cystic adenomatoid malformation of the lung: report of a case.

An 8-year-old male presented with a cystic lung lesion in the left lower lobe, which was initially detected during surgery for a spontaneous rupture of the sigmoid colon at the age of 6 years. Tissue fragility and a tendency to bleed easily were noted during the surgery, which strongly suggested vascular Ehlers-Danlos syndrome. Although there was no abnormality in the hemostasis screening test, or any suspicious hereditary problem in his pedigree, genetic gene testing for vascular Ehlers-Danlos syndrome was recommended, and showed a de novo mutation in the COL3A1 gene. This report presents the case of patient with occlusive vascular Ehlers-Danlos syndrome accompanying a congenital cystic adenomatoid malformation of lung, in addition to a duplicated infrarenal vena cava.

Thoracic air-leak syndromes in hematopoietic stem cell transplant recipients with graft-versus-host disease: a possible sign for poor response to treatment and poor prognosis.

Bronchiolitis obliterans (BO) or bronchiolitis obliterans organizing pneumonia (BOOP) is one of manifestations of graft-versus-host disease (GVHD), a complication of hematopoietic stem cell transplantation (HSCT). Recently there are reports about thoracic air-leakage syndrome (TALS), but real incidence, clinical course, and implications of TALS remain unclear. Retrospective review of 18 TALS patients among 2,177 patients who received allogeneic HSCT between January 2000 to July 2007 was done. Clinical manifestations, treatments, and outcomes of TALS were reviewed. The incidence of TALS was 0.83% (18/2,177). The onset of TALS was mean 425.9+/-417.8 days (60-1,825 days) after HSCT, and the duration was mean 16.3+/-21 days (2-90 days). The most common types of TALS were spontaneous pneumothroax (n=14), followed by subcutaneous emphysema (n=6), pneumomediastinum (n=5), interstitial emphysema (n=2), and pneumopericardium (n=1). TALS persisted in six patients, who died during the same hospitalization. The 12 patients recovered from TALS, but only 2 survived, while others died due to aggravation of GVHD. TALS may complicate BO/BOOP and be an initial manifestation of BO/BOOP. TALS is hard to be resolved, and even after the recovery, patients die because of aggravation of GVHD. We suggest specifically in HSCT patients, when once developed, TALS seems hard to be cured, and as a result, be related to high fatality.

The effect of thoracosopic thoracic sympathetomy on pulmonary function and bronchial hyperresponsiveness.

BACKGROUND: Endoscopic thoracic sympathectic denervation (ESD) is a procedure used in primary hyperhidrosis and upper extremity ischemia. Bronchial tone is affected by the sympathetic and parasympathetic nervous systems and bronchial asthma is associated with an imbalance between them. The aim of this study was to evaluate the effects of ESD on pulmonary function and bronchial hyperresponsiveness (BHR). PATIENTS AND METHODS: Fifty-eight patients with primary hyperhidrosis (n = 54) or upper limb ischemia (n = 4) were included. Spirometry and bronchial provocation test with methacholine was performed before and 4 weeks after ESD. RESULTS: Forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) were significantly decreased early after ESD (from 4.67 +/- 0.84 L and 4.36 +/- 0.85 L to 4.12 +/- 0.78 L and 3.84 +/- 0.82 L, respectively), although no patient complained of an aggravation of respiratory symptoms. Twelve patients (21%) had a positive response to methacholine provocation preoperatively, and all remained positive post surgery. The provocative concentration of methacholine, which brought about a 20% decrease in the FEV(1) in the patients, was not significantly changed after surgery (from 5.1 +/- 4.3 to 4.6 +/- 4.6). Of 46 patients who had a negative result for methacholine challenge preoperatively, 12 (26%) became positive after surgery. In terms of the level of sympathectomy, T3 sympathectomy significantly increased the ratio of patients exhibiting a positive response to methacholine (from 19% to 34%, respectively) (p < 0.005). CONCLUSIONS: Thoracic sympathectomy can adversely affect lung function early after surgery, although the clinical significance is uncertain. It may also exert an influence on the development of bronchial hyperresponsiveness, especially when performed at the T3 level.

Off-pump open pulmonary embolectomy for patients with major pulmonary embolism.

Acute major pulmonary artery embolism (AMPE) requires rapid diagnosis and early intensive treatment to optimize patient outcomes. Most patients with AMPE and hemodynamic instability need open pulmonary embolectomy (OPE). We modified the technique of OPE to include a minimally invasive procedure without the use of cardiopulmonary bypass (CPB). From March 1988 to April 2006, we performed OPE on a total of 12 patients (21 sides) with AMPE. Seven patients (13 sides) underwent conventional OPE with CPB and 5 patients underwent off-pump OPE (OPPE), 4 (8 sides) with AMPE and 1 with catheter embolus with thrombosis. In patients who underwent conventional OPE, there was 1 hospital death in a patient with severe right ventricle dysfunction and 2 significant cases of airway bleeding. In patients who underwent OPPE, there was 1 case of minimal airway bleeding. Mean systolic pulmonary artery pressure in conventional OPE and OPPE patients, respectively, decreased from 50.3 +/- 14 mmHg and 35.4 +/- 6.6 mmHg pre-operatively to 41.7 +/- 20 and 28 +/- 3 mmHg postoperatively. During the long-term follow-up, there were 2 cancer-related deaths but no recurrence of PE. All surviving patients maintained functional class I (n = 10) or II (n = 1). Compared with conventional OPE, OPPE was effective for treating AMPE in our selected cases. Modification of conventional CPB and systemic full heparinization to minimal use of systemic heparinization without CPB may be helpful in treating selected patients with AMPE.