Prognostic impact of a new score using neutrophil-to-lymphocyte ratios in the serum and malignant pleural effusion in lung cancer patients.

BACKGROUNDS: Various studies have reported that the neutrophil-to-lymphocyte ratio in the serum (sNLR) may serve as a cost-effective and useful prognostic factor in patients with various cancer types. However, no study has reported the prognostic impact of the NLR in malignant pleural effusion (MPE). To address this gap, we investigated the clinical impact of NLR as a prognostic factor in MPE (mNLR) and a new scoring system that use NLRs in the serum and MPE (smNLR score) in lung cancer patients. METHODS: We retrospectively reviewed all of the patients who were diagnosed with lung cancer and who presented with pleural effusion. To maintain the quality of the study, only patients with malignant cells in the pleural fluid or tissue were included. The patients were classified into three smNLR score groups, and clinical variables were investigated for their correlation with survival. RESULTS: In all, 158 patients were classified into three smNLR score groups as follows: 84 (53.2%) had a score of 0, 58 (36.7%) had a score of 1, and 16 (10.1%) had a score of 2. In a univariate analysis, high sNLR, mNLR, and increments of the smNLR score were associated with shorter overall survival (p < 0.001, p = 0.004, and p < 0.001, respectively); moreover, age, Eastern Cooperative Oncology Group performance status (ECOG PS), histology, M stage, hemoglobin level, albumin level, and calcium level were significant prognostic factors. A multivariable analysis confirmed that ECOG PS (p < 0.001), histology (p = 0.001), and smNLR score (p < 0.012) were independent predictors of overall survival. CONCLUSIONS: The new smNLR score is a useful and cost-effective prognostic factor in lung cancer patients with MPE. Although further studies are required to generalize our results, this information will benefit clinicians and patients in determining the most appropriate therapy for patients with MPE.

A Systemic Immune Inflammation Index and PD-L1 (SP142) Expression as a Potential Combined Biomarker of the Clinical Benefit of Chemo-Immunotherapy in Extensive-Stage Small-Cell Lung Cancer.

Background: No studies have identified combined biomarkers that may be more reasonable for the assessment of current chemo-immunotherapy in patients with extensive stage small-cell lung cancer (ES-SCLC). Methods: This study was conducted to investigate a combined biomarker with prognostic or predictive value in ES-SCLC. We determined the best independent prognostic biomarker among the four complete blood-count-derived inflammatory biomarkers (CBC-IBs). Subsequently, we analyzed the prognostic or predictive value of combining this independent CBC-IB with PD-L1 (SP142) expression. We prospectively assessed the SP142 analyses in tumor samples at diagnosis. Results: All in all, 55 patients with ES-SCLC were classified into four groups according to the systemic immune inflammation index (SII) (low/high) and SP142 (positive/negative). The best survival was observed in the low-SII/ SP142-positive group, whereas the worst survival was observed in the high-SII/SP142-negative group (p = 0.002). The combined SII-SP142 biomarker was better for predicting both survival and disease progression in patients with ES-SCLC. Conclusions: The combined SII-SP142 biomarker can be readily and universally obtained at a low cost in clinical practice, without requiring advanced genomics technology or specialized expertise. Although further studies are needed to confirm that the combined SII-SP142 biomarker is widely applicable, it should help clinicians to identify the best patients for combined chemotherapy with atezolizumab in ES-SCLC.

Tailored re-roofing technique for pulsatile tinnitus caused by sigmoid sinus dehiscence or diverticulum.

Background: Sigmoid sinus diverticulum/dehiscence (SSD) is one of the treatable causes of venous pulsatile tinnitus. It can be diagnosed using temporal bone computed tomography (CT) or magnetic resonance angiography/venography (MRA). In cases where patients find their symptoms intolerable, surgical treatment is typically preferred. Here, we have presented a novel surgical technique involving sigmoid sinus re-roofing and have analyzed its feasibility. Methods: Between January 2020 and July 2023, approximately 150 patients with pulsatile tinnitus were evaluated at two different tertiary hospitals. Of these, 12 patients were diagnosed with SSD, and seven underwent surgical treatment. Five patients were treated with tailored reroofing (TRR) of the sigmoid sinus and two with transmastoid resurfacing (MRS) of the sigmoid sinus. We compared the Korean tinnitus handicap inventory (K-THI) score, pure tone audiogram (PTA) threshold, and CT findings before and a month after surgeries for these two techniques. The operation time was also analyzed. Results: In TRR cases, the K-THI score reduced from 55.0 ± 31.4 preoperatively to 4.0 ± 3.0 postoperatively, and the SSD was well-repositioned and covered by a bone chip postoperatively. In MRS cases, the K-THI score reduced from 41.0 ± 9.9 preoperatively to 15.0 ± 21.2 postoperatively, and the SSD was well-covered with bone cement postoperatively. The average surgical time of five TRR and two MRS cases were 77.5 ± 32.5 and 174.0 ± 75.0 min, respectively. No complications were noted. Conclusions: Despite the insufficient number of cases, we noted that TRR requires a reasonable amount of time, involves a smaller incision, and may provide favorable outcomes compared to conventional MRS in cases of pulsatile tinnitus associated with SSD. Level of evidence: IV.

Mediastinal lymphangioma treated using endobronchial ultrasound-guided transbronchial needle aspiration.

Lymphangiomas are localized malformations of the lymphatic system that most commonly occur in the head and neck. However, less than 1% of all lymphangiomas are confined to the mediastinum. The standard treatment has been surgical excision, but the involvement of vital structures in the area local to the lymphangioma makes total excision virtually impossible in most cases. To our knowledge, there has been no report of mediastinal lymphangioma treated with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). We report here the first case of safe, effective treatment of a very large mediastinal lymphangioma using EBUS-TBNA in a 29-year-old man.

Fabrication of High-Density Out-of-Plane Microneedle Arrays with Various Heights and Diverse Cross-Sectional Shapes.

Out-of-plane microneedle structures are widely used in various applications such as transcutaneous drug delivery and neural signal recording for brain machine interface. This work presents a novel but simple method to fabricate high-density silicon (Si) microneedle arrays with various heights and diverse cross-sectional shapes depending on photomask pattern designs. The proposed fabrication method is composed of a single photolithography and two subsequent deep reactive ion etching (DRIE) steps. First, a photoresist layer was patterned on a Si substrate to define areas to be etched, which will eventually determine the final location and shape of each individual microneedle. Then, the 1st DRIE step created deep trenches with a highly anisotropic etching of the Si substrate. Subsequently, the photoresist was removed for more isotropic etching; the 2nd DRIE isolated and sharpened microneedles from the predefined trench structures. Depending on diverse photomask designs, the 2nd DRIE formed arrays of microneedles that have various height distributions, as well as diverse cross-sectional shapes across the substrate. With these simple steps, high-aspect ratio microneedles were created in the high density of up to 625 microneedles mm-2 on a Si wafer. Insertion tests showed a small force as low as ~ 172 µN/microneedle is required for microneedle arrays to penetrate the dura mater of a mouse brain. To demonstrate a feasibility of drug delivery application, we also implemented silk microneedle arrays using molding processes. The fabrication method of the present study is expected to be broadly applicable to create microneedle structures for drug delivery, neuroprosthetic devices, and so on.

A Preliminary Study on the Prognostic Impact of Neutrophil to Lymphocyte Ratio of the Bronchoalveolar Lavage Fluid in Patients with Lung Cancer.

The cumulative results indicate that the neutrophil to lymphocyte ratio of peripheral blood (pbNLR) is a useful prognostic factor in patients with various cancers. In contrast to peripheral blood, the bronchoalveolar lavage (BAL) fluid is in direct contact with the lung lesion. However, no study has reported on the clinical utility of the NLR of BAL fluid (bNLR) for patients with lung cancer. To investigate the clinical utility of the bNLR as a prognostic factor in patients with lung cancer, we conducted a retrospective review of the prospectively collected data. A total of 45 patients were classified into high bNLR (n = 29) and low bNLR (n = 16) groups. A high pbNLR and high bNLR were associated with a shorter overall survival (p < 0.001 and p = 0.011, respectively). A multivariable analysis confirmed that ECOG PS (p = 0.023), M stage (p = 0.035), pbNLR (p = 0.008), and bNLR (p = 0.0160) were independent predictors of overall survival. Similar to the pbNLR, a high bNLR value was associated with a poor prognosis in patients with lung cancer. Although further studies are required to apply our results clinically, this is the first study to show the clinical value of the bNLR in patients with lung cancer.

Low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer.

BACKGROUND: The programmed cell death pathway necroptosis may synergize with the DNA damage response (DDR) in opposing tumor progression. While our basic mechanistic understanding of the necroptotic cell death advances rapidly, its prognostic implications have not been thoroughly examined in cancers. METHODS: We included 394 patients with stage I non-small-cell lung cancer (NSCLC) who underwent surgical tumor resection between 1 January 1997 and 31 December 2011 and measured expression levels of nine proteins involved in necroptosis and the DDR in primary samples from 394 patients using tissue microarray. Protein expression evaluated by using an H-score method was dichotomized by the median value. The overall survival as the endpoint was calculated from the time of diagnosis to the time of the last follow-up or death. RESULTS: We find that low-level expression of the necroptosis markers RIPK3 and PELI1 is associated with high risk of patient death. High-level expression of the key DDR factor p53 in combination with low-level expression of either RIPK3 or PELI1 increases the risk further. These gene expression effects appear to occur specifically in the squamous cell carcinoma (SCC) subtype of stage I NSCLC, while not observed in the non-SCC subtypes. CONCLUSIONS: Low-level expression of such necroptosis factors as RIPK3 and PELI1 in combination with high-level expression of the DDR factor p53 can serve as a critical indicator in predicting survival of stage I NSCLC patients with the SCC subtype.

Diagnosis of pulmonary cement embolism using only the bone window setting on computed tomography: a case report.

Pulmonary cement embolism (PCE) is one of several complications of percutaneous vertebroplasty and kyphoplasty. Generally, PCE can be easily diagnosed based on typical chest radiograph findings such as single or multiple radiographically dense opacities with a tubular or branch shape in the lung field along with a recent history of percutaneous vertebroplasty or kyphoplasty. These findings can be alarming and may be encountered on routine chest radiographs, even in asymptomatic patients. One study showed that PCEs that were not visualized on chest radiograph were also not shown on chest computed tomography. However, we encountered a patient with dyspnea who had normal chest radiograph findings but was diagnosed with PCE through only the bone window setting on chest computed tomography. The present case will be beneficial to all physicians examining older patients with dyspnea.

The optimal sequence of bronchial brushing and washing for diagnosing peripheral lung cancer using non-guided flexible bronchoscopy.

The optimum sequence of bronchial brushing and washing for diagnosing peripheral lung cancer, defined as an invisible endobronchial tumour, is not clear and requires further study. We prospectively obtained washing samples after brushing in patients with peripheral lung tumours during non-guided flexible bronchoscopy (FB) to investigate the diagnostic yield of these samples and conducted a retrospective review of the prospectively collected data. The study included 166 patients who met the inclusion criteria. The overall diagnostic yield of bronchial brushing and washing for peripheral lung cancer was 52.4%. The diagnostic yields of brushing and washing were 37.3% and 46.4%, respectively, and that of washing was superior according to McNemar's test (p = 0.017, κ = 0.570). Furthermore, washing was diagnostic, whereas brushing was not, in 15.1% of all cases. Comparison of positive washing cytology (brushing) with the respective pathological diagnosis yielded a concordance rate of 88.3% (90.3%), with κ = 0.769 (0.801) (p < 0.001). Performing washing after brushing during non-guided FB is a very safe, cost-effective procedure that may help improve the diagnostic yield in patients with suspected peripheral lung cancer. Our information will also benefit clinicians performing diagnostic bronchoscopy in patients with suspected peripheral lung cancer when fluoroscopic guidance or advanced bronchoscopy techniques are not available.

Dramatic response of acute disseminated intravascular coagulation to erlotinib in a patient with lung adenocarcinoma with activating EGFR mutation.

Disseminated intravascular coagulation (DIC) is a commonly encountered clinical situation characterized by thrombotic occlusion or bleeding in patients with lung cancer. DIC in patients with cancer is usually asymptomatic, taking a chronic form as a compensatory mechanism. Although acute DIC in patients with lung cancer is rarely reported, it can be fatal. We herein describe a patient with lung adenocarcinoma with an activating mutation of the epidermal growth factor receptor (EGFR) gene who developed acute DIC after minor surgical excision. The patient's condition dramatically improved immediately after administration of erlotinib. This report alerts physicians to the occurrence of acute DIC and serves as a reference in treating EGFR mutation-positive lung cancer in patients with DIC.

Small-cell Lung Cancer Presenting as Fatal Pulmonary Hemorrhage.

Small-cell lung cancer (SCLC) is a lung cancer histological subtype unusual in its favorable response to cytotoxic chemotherapy. Life-threatening manifestations at presentation are rarely reported and should be an important clinical concern. We report a case of a 63-year-old man presenting with rapid-onset refractory severe thrombocytopenia, development of massive hemoptysis, and death from respiratory failure. This case provides clinicians a reference for this unusual presentation and carries clinical implications for managing SCLC patients.

Natural history and therapeutic implications of patients with catamenial hemoptysis.

Evidence as to whether clinician has to give specific treatment in all patients of catamenial hemoptysis is unclear. We considered that the current treatment such as long-term usage of hormonal agent or surgery might be excessive for the catamenial hemoptysis. Therefore, we developed prospective observation study with observation strategy and follow-up for the patients. In sequential four patients of catamenial hemoptysis between December 2000 and November 2001, physical examination, chest X-ray, pelvic ultrasonogram and chest CT scan were taken at both the diagnosis and last follow-up. All patients were only observed without specific treatment within the limit of the possibility and followed for average 58 months. Mean age of patients was 23.5years (range, 22-25years). All patients have a history of undertaking one or two dilatations and curettages before diagnosis. The chest CT scans of all patients presented with ground-glass opacities of peripheral location that were disappeared without any residual lesion at last follow-up. Hemoptysis of two patients was spontaneously disappeared after 6 months. In the other two patients, it was greatly lessened in amount and frequency, then clinically insignificant in one. It was disappeared after subsequent 2 months and then relapsed two times in the late of follow-up of another patient. This study suggests that observation only may be an alternative option in the treatment of catamenial hemoptysis.

Effect of ERCC1 polymorphisms and the modification by smoking on the survival of non-small cell lung cancer patients.

A few reports for ERCC1 SNPs were conducted in patients treated with cisplatin chemotherapy. The aim of this study is to determine whether the SNPs are a prognostic factor related to the treatment or not and if smoking level of the patients have any relationship to the SNPs' effect on the survival. Peripheral blood lymphocytes of 423 consecutive non-small cell lung cancer patients were examined: 245 of the patients received cisplatin combination chemotherapy and 178 received only conservative care. We examined ERCC1 SNPs (codon 118 C/T and 8092 C/A). Whereas ERCC1 118 SNP had no effect on the survival in patients' given no treatment, an effect of the SNP was observed in the treatment group, especially in stage III. When smoking was considered, the risk effect of the T allele was shown to be significantly associated with the group that had more than 50 pack yr (p=0.03). As for the ERCC1 8092 C/A, no significant effects were observed in the treated group and the non-treatment group. These findings may suggest that the ERCC1 118 SNP is an useful prognostic factor related to cisplatin therapy and the effect of this polymorphism appears to be modified by smoking.

A case of pulmonary cryptococcosis with non-small cell lung cancer in idiopathic CD4+ T-lymphocytopenia.

Cryptococcus neoformans commonly causes opportunistic infections in immunocompromised patients, especially in patients with AIDS. CD4+ T-lymphocytopenia in AIDS indicates an increased risk of opportunistic infection and a decline in immunological function. Idiopathic CD4 T-lymphocytopenia (ICL) is characterized by depletions in the CD4+ T-cell subsets, without evidence of HIV infection. Immunodeficiency can exist in the absence of laboratory evidence of HIV infection, and T-cell subsets should be evaluated in patients who present with unusual opportunistic infections. We report a case of pulmonary cryptococcosis and lung cancer in a patient with persistently low CD4+ cell counts, without evidence of HIV infection.

Migratory eosinophilic alveolitis caused by radiation therapy.

Although radiation pneumonitis is usually confined to irradiated areas, some studies have reported that radiation-induced lymphocytic alveolitis can also spread to the non-irradiated lung. However, there have been few reports of radiation-induced eosinophilic alveolitis. We report the case of a 27-year-old female with radiation pneumonitis, occurring 4 months after radiation therapy for cancer of the left breast. Clinical and radiological relapse followed withdrawal of corticosteroids. Examination of bronchoalveolar lavage (BAL) in patchy airspace consolidations revealed increased eosinophil counts. Finally, clinical and radiological signs resolved rapidly after reintroduction of corticosteroids. Eosinophilic alveolitis may be promoted by radiation therapy. In the present case report, possible mechanisms for radiation-induced eosinophilic alveolitis are also reviewed.

Massive hemoptysis after generalized tonic clonic seizure requiring mechanical ventilation.

A 38-year-old woman presented with massive hemoptysis (>200 mL/ 24 hours) occurring abruptly after generalized tonic clonic seizure. She experienced similar episodes of hemoptysis on three later occasions. Although the coexistence of hemoptysis and seizure has been reported, albeit rarely, as a clinical manifestation of postictal neurogenic pulmonary edema, massive hemoptysis after seizure is an extremely rare event with no recurrent cases of such episodes having ever been reported. The coexistence of hemoptysis and seizure increases the difficulty in diagnosis for the clinician. We describe the differential diagnosis among the diseases capable of causing seizure and hemoptysis.

The effects of urokinase instillation therapy via percutaneous transthoracic catheter in loculated tuberculous pleural effusion: a randomized prospective study.

The purpose of this study was to propose that intrapleural urokinase (UK) instillation could reduce pleural thickening in the treatment of loculated tuberculous pleural effusion. Forty- three patients who were initially diagnosed as having loculated tuberculous pleural effusion were assigned at random to receive either the combined treatment of UK instillation including anti-tuberculosis agents (UK group, 21 patients) or strictly the unaccompanied anti-tuberculous agents (control group, 22 patients). The UK group received 100,000 IU of UK dissolved in 150 ml of normal saline daily, introduced into the pleural cavity via a pig-tail catheter. The control group was treated with anti-tuberculous agents, excepting diagnostic thoracentesis. After the cessation of treatment, residual pleural thickening (RPT) was compared between the two groups. Clinical characteristics and pleural fluid biochemistry were also evaluated. The RPT (4.59 +/- 5.93 mm) of the UK group was significantly lower than that (18.6 +/- 26.37 mm) of the control group (p < 0.05). The interval of symptoms observed prior to treatment of patients with RPT > or = 10 mm (6.0 +/- 3.4 wks) was detected to be significantly longer than in those with RPT < 10 mm (2.1 +/- 1.2 wks) in the control group (p < 0.05). However, there were no discernible differences were seen in the pleural fluid parameter in patients with RPT > or = 10 mm, as compared to patients with RPT < 10 mm in the UK group. These results indicate that the treatment of loculated tuberculous pleural effusion with UK instillation via percutaneous transthoracic catheter can cause a successful reduction in pleural thickening.

Acute respiratory distress syndrome induced by adenovirus in an otherwise healthy woman.

Acute respiratory distress syndrome (ARDS) caused by adenovirus is a rare event in healthy adults, especially in non- military settings. Although treatment with intravenous ribavirin has been reported, supportive care, including mechanical ventilation, is known to be the main stay in the treatment of ARDS caused by adenovirus, with high-dose steroid treatment having rarely been reported. We report our experience with a 41-year-old, otherwise healthy, woman with ARDS, treated with high-dose steroid and mechanical ventilatory support.

Pancreaticothoracic fistula presenting with hemoptysis and pneumothorax in a chronic alcoholic patient.

Pancreaticothoracic fistula is a rare complication of acute or chronic alcoholic pancreatitis. It may present with various symptoms, like dyspnea, abdominal pain, cough, chest pain, fever, back pain, hemoptysis, fatigue, or orthopnea. Pancreaticothoracic fistula can be detected by magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or computed tomography. MRCP has high sensitivity and fewer side effects, and thus it has recently been recommended as the first choice for the detection of pancreaticothoracic fistula. On the other hand, ERCP enables the detection and treatment of pancreaticothoracic fistula and allows for stent insertion; for this reason it is a commonly used modality in pancreaticothoracic fistula cases. Herein, the authors describe a case of pancreaticothoracic fistula detected by ERCP and MRCP that manifested only respiratory symptoms, namely hemoptysis and pneumothorax without abdominal pain, which commonly accompanies pancreatitis.

Multiple hypercoagulability disorders at presentation of non-small-cell lung cancer.

Hypercoagulability disorders are commonly encountered in clinical situations in patients with a variety of cancers. However, several hypercoagulability disorders presenting as first symptoms or signs in cancer patients have rarely been reported. We herein described a case of a woman with adenocarcinoma of the lung presenting with deep vein thrombosis, nonbacterial thrombotic endocarditis, recurrent cerebral embolic infarction, and heart failure.