Taste disorder in a patient with invasive thymoma without myasthenia gravis: a rare case report.

Taste disorder has been reported as a non-motor symptom caused by myasthenia gravis (MG)-related autoimmune mechanism. Taste disorder in some cases recovered along with MG treatment, such as thymothymectomy or immunosuppressive treatment. However, symptom of taste disorder in thymoma patients without MG is very rare. Here, we reported a case of invasive thymoma without MG which had concurrent taste disorder. The taste disorder was successfully treated with cyclosporine. A female in her seventies had an anterior mediastinal tumor of 78-mm in diameter and pleural dissemination. She also had taste disorder, limited to sweet taste, and pure red cell aplasia (PRCA). Symptoms and physical findings showed no feature of MG. Pre-operative blood examination revealed no elevation of anti-acetylcholine receptor antibody . Extended total thymothymectomy and resection of all detectable pleural disseminations was performed. Pathological examination showed type B3 thymoma. Clinical stage was Masaoka stage IVa. After operation, there was no improvement in taste disorder and PRCA. Six months after operation, cyclosporine was administered for PRCA. In parallel with gradual improvement of anemia, taste disorder also gradually improved. Three months after the first administration of cyclosporine, taste disorder had completely recovered. This is the first case of taste disorder without any myasthenic status, which recovered with immunosuppressive drug. Our case suggested the potency of immunosuppressive treatment for taste disorder associate with thymoma without MG.

Comprehensive expressional analysis of chemosensitivity-related markers in large cell neuroendocrine carcinoma of the lung.

OBJECTIVES: Various drug-sensitivity markers have been reported to be associated with tumor progression and chemotherapy resistance. Detailed expression profiles of sensitivity markers for cytotoxic chemotherapy in pulmonary large cell neuroendocrine carcinoma (LCNEC) remain unclear. Herein, we aimed to clarify the correlation between the expression of drug-sensitivity markers and clinicopathological features, prognostic impact, and status of tumor immunity in patients with LCNEC. METHODS: We retrospectively analyzed the correlation between clinicopathological features and the expression of drug-sensitivity-related markers, including vascular endothelial growth factor 2 (VEGFR2), thymidylate synthase (TS), tubulin beta 3 class III (TUBB3), topoisomerase I (Topo-I), and Topo-II in 92 surgically resected LCNEC samples. Furthermore, we examined the prognostic significance of expression of these and their correlation with the immune cell status. RESULTS: Overall, high expression of TS, TUBB3, VEGFR2, Topo-I, and Topo-II was detected in 50 (54%), 31 (34%), 23 (25%), 65 (71%), and 36 (39%) samples, respectively. Univariate and multivariate analyses revealed that advanced pathological T and N factors, positive lymphatic permeation, and Topo-II expression were independent unfavorable prognosticators for recurrence-free survival, and advanced pathological T and N factors, Topo-II positive expression, and TS positive expression were independent unfavorable prognosticators for overall survival. In terms of correlation with immune cell status, higher expression of VEGFR2 was closely linked to negative PD-L1 expression. CONCLUSIONS: These findings suggest that elevated Topo-II and TS expression may contribute to poor outcomes through protumoral biology in patients with LCNEC, and elevated VEGFR2 expression might negatively impact tumor immune reactions in LCNEC.

Author Correction: Butterfly-shaped magnetoresistance in triangular-lattice antiferromagnet Ag2CrO2.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Butterfly-shaped magnetoresistance in triangular-lattice antiferromagnet Ag2CrO2.

Spintronic devices using antiferromagnets (AFMs) are promising candidates for future applications. Recently, many interesting physical properties have been reported with AFM-based devices. Here we report a butterfly-shaped magnetoresistance (MR) in a micrometer-sized triangular-lattice antiferromagnet Ag2CrO2. The material consists of two-dimensional triangular-lattice CrO2 layers with antiferromagnetically coupled S = 3/2 spins and Ag2 layers with high electrical conductivity. The butterfly-shaped MR appears only when the magnetic field is applied perpendicularly to the CrO2 plane with the maximum MR ratio (≈15%) at the magnetic ordering temperature. These features are distinct from those observed in conventional magnetic materials. We propose a theoretical model where fluctuations of partially disordered spins with the Ising anisotropy play an essential role in the butterfly-shaped MR in Ag2CrO2.

Pulmonary Artery Compression Facilitates Intersegmental Border Visualization.

Intravenous indocyanine green injection is useful for the identification of the intersegmental border by infrared thoracoscopy during anatomic segmentectomy. However, surgeons encounter cases in which visualization of the intersegmental border is difficult. In particular, intravenous indocyanine green fluorescence in the upper lobe is occasionally obscured by to the relatively lesser blood flow in the upper lobe pulmonary arteries. This report describes an interlobar pulmonary artery compression method that is a simple and effective technique for clearly visualizing the intersegmental border through infrared thoracoscopy with intravenous indocyanine green during upper lobe segmentectomy.

Prognostic significance of PD-L1 expression and tumor infiltrating lymphocytes in large cell neuroendocrine carcinoma of lung.

OBJECTIVES: Since large cell neuroendocrine carcinoma (LCNEC) is a relatively rare histologic type of primary lung cancer, little is known about the immunological status of patients with LCNEC. We aimed to clarify the expression and prognostic impact of programmed cell death ligand 1 (PD-L1), CD8, CD4, and Forkhead box protein P3 (Foxp3) in LCNEC. METHODS: We retrospectively analyzed PD-L1, CD8, CD4, and Foxp3 expressions in 95 surgically resected LCNEC. PD-L1 positive staining was determined in tumors with more than 1% of tumor cells stained to any intensity, and CD8, CD4, and Foxp3 positivity was determined in tumors with more than 5% of lymphocytes stained. RESULTS: Positive expression of PD-L1, CD8, CD4, and Foxp3 was observed in 70 (74%), 52 (55%), 76 (80%), and 43 (45%) tumors, respectively. The expression of PD-L1 was significantly correlated with positive lymphatic permeation. Positive correlations were mutually observed among tumor infiltrating immune cells. Univariate and multivariate analyses showed that positive pleural invasion and Foxp3 negative expression were independent unfavorable prognostic factors for overall survival (OS). Advanced pathological stage, positive pleural invasion, CD4 negative expression in cancer stroma, and Foxp3 negative expression were identified as independent unfavorable prognostic factors for recurrence free survival (RFS). CONCLUSIONS: Foxp3 positive tumor infiltrating lymphocytes (TILs) were an independent favorable prognostic factor for both OS and RFS, whereas CD4 positive TILs were an independent significant unfavorable prognostic factor for RFS. The high frequency of PD-L1 expression could support the use of anti-programmed cell death 1 antibody in the treatment of LCNEC.

[Multidisciplinary Approach to Recurrence after Resection of Primary Lung Cancer].

BACKGROUND: The standard approach for treating recurrence after complete resection of primary non-small cell lung cancer has been controversial. We present here a multidisciplinary strategy for postoperative recurrence in patients with primary lung cancer. PATIENTS AND METHODS: Over the last 7 years, we examined the disease-free survival and overall survival of 70 patients who underwent multidisciplinary treatment for recurrence after surgical resection of primary lung cancer. RESULTS: The median overall survival was 32.3 months after surgery and 17.4 months after recurrence developed, indicating significantly better prognoses in females and in patients with adenocarcinoma, stage I disease, driver mutation positivity, a longer postoperative disease-free period, and never smokers. Eight patients survived more than 5 years after recurrence;of these patients, all had adenocarcinomas, 7 had oligometastases and/or tumor dormancy, and 5 received multiple-drug regimens. CONCLUSION: Multidisciplinary treatment for recurrence after resection of primary lung cancer was effective for patients receiving various drug regimens. In patients with oligometastases, disease control was achieved by a combination of local treatments targeting each involved organ. In patients with tumor dormancy, follow-up or a drug holiday was important to maintain the patient's quality of life.

Thoracoscopic lateral and posterior basal (S9 + 10) segmentectomy using intersegmental tunnelling.

The appropriate lateral and posterior basal (S9 + 10) segmentectomy requires exposure and recognition of common basal pulmonary vein branches located deeply in the lung parenchyma. Therefore, we applied the intersegmental tunnelling method in S9 + 10 segmentectomy to recognize the dominant veins to the S9 + 10 segment accurately. Between April 2014 and December 2015, five patients underwent thoracoscopic S9 + 10 segmentectomy using intersegmental tunnelling. By using this technique, we can recognize the branches of the pulmonary vein to the affected S9 + 10 segment accurately. This technique can let us perform appropriate S9 + 10 segmentectomy.

Paraspinous muscle flap for the treatment of an empyema cavity: three case reports.

A surgical option is commonly chosen when conservative medical therapy for empyema is impossible. The muscles used include the latissimus dorsi, trapezius, and pectoris major, based on the size and location of the empyema cavity. However, these volumes are decreased in patients suffering from malnutrition, and flap dissection and elevation are sometimes invasive. Therefore, we developed an alternative method, and present three successful cases in which we used a pedicled paraspinous muscle flap to fill the dead space caused by empyema fenestration in the medial region of the back. The paraspinous muscle flap remains an important tool in reconstruction. However, such flaps should be created only in selected cases, such as those with empyema in the posterior region. Also, if the pleural space is large, additional muscle flaps will be required.

Troubleshooting for bleeding in thoracoscopic anatomic pulmonary resection.

Introduction The objective of this study was to evaluate intraoperative vessel injury and assess troubleshooting during thoracoscopic anatomic pulmonary resection. Methods Between April 2012 and March 2016, 240 patients underwent thoracoscopic anatomic lung resection, 26 of whom were identified as having massive bleeding intraoperatively. We analyzed the injured vessel and the hemostatic procedure employed, then compared the perioperative outcomes in patients with ( n = 26) and without ( n = 214) vessel injury. In addition, we compared perioperative results based on the period when surgery was performed: early period: April 2012 to March 2014 ( n = 93) or late period: April 2014 to March 2016 ( n = 146). Results The surgical procedures included 20 lobectomies and 6 segmentectomies. One of the 26 patients had vessel injury at 2 points, giving a total of 27 points of injury. Hemostasis was mostly achieved by application of thrombostatic sealant (63.0%). There were no significant differences in the length postoperative hospitalization ( p = 0.67) or morbidity rate ( p = 0.43) between the vessel injury and the no-vessel injury groups. There were no significant differences in the incidence of significant intraoperative bleeding ( p = 0.13) and total blood loss ( p = 0.13) between the early and late periods. Conclusions Application of thrombostatic sealant is one of the useful methods to achieve hemostasis during thoracoscopic anatomic pulmonary resection. Vascular hazards are inherent to a thoracoscopic approach. Therefore, thoracic surgeons should always be concerned about significant intraoperative bleeding and treat it appropriately.

A convenient method for identifying a small pulmonary nodule using a dyed swab and geometric mapping.

BACKGROUND: Computed tomography (CT)-guided lung needle marking is useful to identify pulmonary nodules. However, certain complications sometimes trigger severe after-effects or death. So, we present a convenient and safe method by which small pulmonary nodules can be identified using a particular dye [2% (w/v) gentian violet]. METHODS: A patient is initially placed in the lateral operative position. Under CT guidance, a "magic marker" is used to identify the skin above the pulmonary nodule. During the operation, the chest wall is punctured on that mark using a needle loop retractor (Mini Loop Retractor II). A swab saturated in the dye solution is attached to a silk thread and passed through the loop. The loop and string are subsequently retracted. The dye-stamp is apparent on the lung surface above the nodule after the lung is inflated. If the scapula, any vertebra, or the clavicle compromised access to a nodule, we used our geometric technique to locate that nodule. RESULTS: We used this technique to treat 51 lesions of 50 patients presenting from 2013 to 2015. Mean tumor diameter was 7 mm. All lesions were identified via thoracoscopy, all nodules were constrained by ring forceps, and wedge resections were performed using a stapler. All lesions lay very close to the staple markings, as judged by finger or instrument palpation. No complications were encountered. CONCLUSIONS: The advantages of our technique are that it is simple and easy, air emboli are not an issue, the skin marking is rapid, safety is assured, and the skin marking does not require hospitalization. Our method is also useful such as following situations; it defines the margins of the cut line upon anatomical segmentectomy, indicates where a skin incision is required, and identifies impalpable nodules, which aids the lung resection but provides frozen sections to the pathologist.

Successful treatment of a bronchopleural fistula after en masse lobectomy.

A 72-year-old man underwent en masse lobectomy of the lower left lobe because of continued hemoptysis. We chose en masse lobectomy as a last resort because the patient had cardiopulmonary problems including chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and continued hemoptysis. The patient developed a bronchopleural fistula 2 weeks later, so the Clagett window procedure was performed. After gauze exchange and cleaning of the pleural space, the Clagett window was closed using a latissimus dorsi muscle flap. He was discharged about 3 months after the initial operation. One of the most critical complications after en masse lobectomy is a bronchopleural fistula because the bronchial stump and vessel are too close to each other. The space between the bronchus and vessel can fill with tissue, such as pulmonary parenchyma or lymph nodes, which cover the fistula.

The optimal starting point for survival time in pulmonary metastasectomy.

AIM: Studies of metastatic lung cancer have used various starting points for calculating the survival period, including the time of primary tumor resection and the first and final pulmonary metastasectomy. This study examined differences in prognostic factors according to the starting point used to calculate survival time. METHODS: We performed surgical resection of pulmonary metastases in 202 consecutive patients between 1999 and 2013. Of these, 146 (excluding overlapping cases) underwent pulmonary metastasectomy. We examined the survival period after resection in patients with pulmonary metastases (group M) and primary tumors (group P). The prognostic influence of variables on survival was analyzed. RESULTS: The 5-year survival rate was 76.7% in group P and 62.0% in group M. The significant prognostic factors were the disease-free interval (>1 and >2 years) in group P, and maximum tumor diameter in group M. Interestingly, multivariate analysis showed that the significant prognostic factors (age and nodule diameter) were identical in both groups. CONCLUSIONS: We believe that the potential confounding factors were counterbalanced by the effect of prognostic factors on multivariate analysis in patients undergoing pulmonary metastasectomy. If the survival period is defined as starting from the time of the primary tumor resection, this may resolve the variance in survival, because pulmonary metastasectomy is only one option among several available treatments.

Surgical treatment for elderly patients with secondary spontaneous pneumothorax.

OBJECTIVES: Our objective was to evaluate the validity of surgery for secondary spontaneous pneumothorax (SSP) by comparison with other treatments or with perioperative results for primary spontaneous pneumothorax (PSP). METHODS: Between January 2009 and March 2015, 144 patients with SSP, aged 60 years or over, were treated in our institution. We reviewed the patients' characteristics, perioperative results, and relapse rate. Treatment to arrest air-leakage included surgery (n = 79), drainage only (n = 30), and pleurodesis (n = 35), and the pneumothorax relapse rate or mortality before discharge was compared for each. Additionally, we compared the perioperative results or relapse rate between SSP (n = 70) and PSP (n = 70) in patients who underwent 3-port thoracoscopic surgery. RESULTS: There was a significant difference in the relapse rate between the surgery and non-surgery groups (5.3 vs. 27.4 %, p = 0.0006). However, no significant difference in mortality before discharge was determined (p = 0.66). Significant differences were identified between the SSP and PSP groups for operation time, duration of chest drainage, and the length of postoperative hospitalization, and the postoperative morbidity were greater in the SSP group (p < 0.0001 for all). However, there was no significant difference in postoperative 30-day mortality or the relapse rate (p = 0.5, p = 0.68, respectively). CONCLUSIONS: Surgical treatment under general anesthesia for SSP is effective for arresting persistent air leaks or avoiding pneumothorax relapse, compared with drainage or pleurodesis, and is feasible if the appropriate perioperative management is performed.

[Perioperative Oral Management of Lung Cancer Patients; Medical, Dental, and Regional Dental Clinic Collaboration].

PURPOSE: To prevent oral problems in lung cancer patients, dental intervention should be performed in conjunction with cancer treatment in cancer base hospitals. This paper reports on the perioperative oral care management of lung cancer patients. PATIENTS AND METHODS: From January 2013 to August 2015, perioperative oral management was performed in 123 patients undergoing pulmonary lobectomy. We ensure cooperation between the departments of medicine and dentistry. First, the dentist plans oral management based on the patient's individual oral status. Then, the actual oral management is performed by an in-hospital dentist and at the regional dental clinic. RESULTS: The patients comprised 70 males and 53 females with an average age of 69.4 years;118 had primary lung cancer and 5 had metastatic lung cancer. Abnormal findings were detected in approximately 50% of the patients, of whom 6 received oral treatment before starting their cancer treatment. Two patients(1.3%)had postoperative complications. In all cases, the oral care support team provided both tooth and oral mucosal care. CONCLUSION: About half of the referred patients required oral treatment. There were no serious adverse events due to the oral care intervention. Further investigation is necessary to establish appropriate treatment policy guidelines for dental disease requiring oral maintenance.

Anterior Uveitis Caused by Ocular Side Effects of Afatinib: A Case Report.

Afatinib is a second-generation epidermal growth factor receptor (EGFR) inhibitor that has been shown to be effective against EGFR-mutated non-small cell lung cancer (NSCLC) resistant to conventional EGFR inhibitors such as gefitinib and erlotinib. Although ocular side effects of gefitinib and erlotinib have been reported, those for afatinib have yet to be definitively established. This report presents details on the first case of unilateral iridocyclitis associated with the side effects of afatinib therapy. A 75-year-old Japanese male ex-smoker with EGFR-mutated NSCLC underwent afatinib therapy for multiple metastases. At 2 weeks, bilateral conjunctivitis developed. Topical medication and a 1-week afatinib washout period resulted in the improvement of the conjunctivitis. However, 3 days after the resumption of afatinib, the patient developed unilateral granulomatous anterior uveitis in his right eye. Best-corrected visual acuity (BCVA) measurement indicated a decimal visual acuity of 0.2, while the slit-lamp findings were characterized by granulomatous inflammation, keratic precipitates, Koeppe nodules and posterior synechiae. There was no evidence suggesting other intraocular inflammatory disease or metastatic tumor. The left eye was intact. The use of topical medication including steroids and a washout of afatinib resulted in a gradual subsiding of the anterior uveitis. After resolution of the anterior uveitis, oral afatinib was resumed. BCVA of the right eye finally recovered to a decimal acuity of 1.0. Ophthalmologists should be aware of the possibility that side effects associated with afatinib could cause granulomatous anterior uveitis.

The efficacy of thoracoscopic fissureless lobectomy in patients with dense fissures.

BACKGROUND: Prolonged air leakage after a lobectomy remains a frequent complication in patients with dense fissures. To avoid postoperative air leakage, we used the "thoracoscopic fissureless technique" for patients with dense fissures. A thoracoscopic approach is useful for the fissureless technique because it gives a good operative view from various angles without dividing the fissure. In this study, we compared the peri- or intraoperative results of thoracoscopic fissureless lobectomies to traditional lobectomies with fissure dissection for pulmonary artery (PA) exposure in order to identify the efficacy of thoracoscopic fissureless lobectomy. METHODS: Between April 2012 and November 2015, 175 patients underwent a thoracoscopic lobectomy with three or four ports, of whom 14 underwent a fissureless lobectomy because of dense fissures. We compared the characteristics and perioperative outcomes of the patients who underwent the fissureless technique (fissureless technique group, n=14) and the traditional fissure dissection technique for PA exposure (traditional technique group, n=161). In our department, fissureless lobectomy is indicated for patients with a fused fissure (fissural grade III or IV as proposed by Craig in 1997) or inflammation makes it difficult to expose the PA, while the traditional technique is used for other patients. RESULTS: Although the fissureless technique group had longer operation time than the traditional technique group (P=0.0045), there was no significant inter-group difference about blood loss (P=0.85), occurrence rate of intraoperative massive bleeding (P=0.6) or conversion rate to thoracotomy (P=0.31). According to postoperative results, there was no significant inter-group difference in duration of chest tube drainage (P=0.56), length of postoperative hospital stay (P=0.14), or morbidity rate (P=0.16). No mortality occurred in either group. CONCLUSIONS: A thoracoscopic fissureless lobectomy is feasible and safe, and useful to avoid postoperative air-leakage in patients with dense fissures.