Combination of Juzentaihoto and chemotherapy improves the prognosis of patients with postoperative recurrence of non-small cell lung cancer.

Kampo medicines have been used to reduce chemotherapy-induced adverse events. However, whether Kampo medicine can improve the prognosis of cancer remains unclear. The present study aimed to clarify the effect of Juzentaihoto (TJ-48) on patients with postoperative recurrence of non-small cell lung cancer. In total, 45 patients with postoperative recurrent non-small cell lung cancer scheduled for first-line chemotherapy were enrolled in the present study. Differences in progression-free survival between the chemotherapy combined with TJ-48 and chemotherapy only groups were analyzed. Body weight change and prognostic nutritional index were also evaluated to examine whether these factors were influenced by TJ-48 administration. Multivariate analysis was performed to detect independent prognostic factors. A significant increase was observed in progression-free survival in the chemotherapy plus TJ-48 group compared with in the chemotherapy alone group (P<0.001). Significant decreases in body weight and prognostic nutritional index score were observed in the chemotherapy alone group (P<0.01 and P<0.05, respectively); however, these decreases were not observed in the chemotherapy plus TJ-48 group. Multivariate analysis revealed that TJ-48 administration with chemotherapy was an independent prognostic factor. In conclusion, TJ-48 combined with chemotherapy may improve the progression-free survival of patients with postoperative recurrence of non-small cell lung cancer by preventing nutritional disorders.

Effect of lidocaine cream analgesia for chest drain tube removal after video-assisted thoracoscopic surgery for lung cancer: a randomized clinical trial.

BACKGROUND AND OBJECTIVES: Pain management makes an important contribution to good respiratory care and early recovery after thoracic surgery. Although the development of video-assisted thoracoscopic surgery (VATS) has led to improved patient outcomes, chest tube removal could be distressful experience for many patients. The aim of this trial was to test whether the addition of lidocaine cream would have a significant impact on the pain treatment during chest tube removal from patients who had undergone VATS for lung cancer. METHODS: This clinical trial was a double-blind randomized study. Forty patients with histologically confirmed lung cancer amenable to lobectomy/segmentectomy were enrolled. All patients had standard perioperative care. Patients were randomly assigned to receive either epidural anesthesia plus placebo cream (placebo, Group P) or epidural anesthesia plus 7% lidocaine cream cutaneously around the chest tube insertion site and on the skin over the tube's course 20 min (Group L) before chest drain removal. RESULTS: Visual analog scale (VAS) scores were higher in Group P (median 5, IQR, 3.25-8) than in Group L (median 2, IQR, 1-3). Pain intensities measured using a PainVision system were also higher in Group P (median 296.7, IQR, 216.9-563.5) than Group L (median 41.2, IQR, 11.8-97.0). VAS scores and the pain intensity associated with chest drain removal were significantly lower in Group L than Group P (p=0.0002 vs p<0.0001). CONCLUSION: Analgesia using lidocaine cream is a very simple way to reduce the pain of chest tube removal after VATS. TRIAL REGISTRATION NUMBER: UMIN000013824.

Reagent-saving immunohistochemistry for HER2 using non-contact alternating current electric field mixing.

AIMS: Human epidermal growth factor receptor 2 (HER2)-targeted agents are an effective approach to treating patients with HER2-positive breast cancer. However, the lack of survival benefit in HER2-negative patients, as well as the toxic effects and high cost of the drugs, highlight the need for accurate and prompt assessment of HER2 status. Our aim was to evaluate the clinical utility of a novel reagent-saving immunohistochemistry method (AC-IHC) that saves HER2 antibody by taking advantage of the non-contact mixing effect in microdroplets subjected to an alternating current electric field. METHODS: Ninety-five specimens were used from patients diagnosed with primary breast cancers identified immunohistochemically as HER2 0/1+, 2+ or 3+ using ASCO/CAP guideline-certified standard IHC. The specimens were all tested using the conventional IHC method (1:50 antibody dilution) as well as AC-IHC (1:50 dilution) and reagent-saving AC-IHC (1:100 dilution). RESULTS: The reagent-saving AC-IHC produced stable results with less non-specific staining using smaller amounts of labelled antibody. Moreover, the staining and accuracy of HER2 status evaluated with the reagent-saving AC-IHC method was equal to that achieved with standard IHC. CONCLUSIONS: These results suggest reagent-saving AC-IHC could be used as a clinical tool for accurate and stable HER2 IHC, even when reagent concentrations vary.

[Antineutrophil Cytoplasmic Antibody (ANCA) Negative Limited-form Granulomatosis with Polyangiitis of the Lung Diagnosed by the Thoracoscopic Lung Biopsy].

Antineutrophil cytoplasmic antibody (ANCA) negative pulmonary limited-form granulomatous with polyangiitis (GPA) is a rare type of GPA. A 53-year-old female had been followed as the possible pulmonary infarction of bilateral lungs for 4 years without any therapy. Chest computed tomography(CT) examination of the patient showed newly appeared nodular lesions in the lungs, which were suspected as malignancy by positron emission tomography (PET) -CT. Thoracoscopic lung biopsy of the lesions was performed and histopathological diagnosis was GPA showing multiple granulomas with vasculitis. Since both C and P-ANCA were negative and no evidence of kidney involvement, we finally diagnosed the lung lesions as ANCA negative limited-form GPA.

Case of advanced pulmonary squamous cell carcinoma cured by resection through preoperative induction of immune checkpoint inhibitor.

The options for lung cancer treatment have increased due to the development of immune checkpoint inhibitors, but there has been no report of inoperable cases whereby the treatment effects rendered the case operable, an operation was subsequently performed, and histological assessment of the surgical specimen was carried out. Here, we report a 67-year-old man who was given pembrolizumab for T3N0 lung squamous cell carcinoma suspected of pericardial infiltration and judged inoperable. Treatment effect was evaluated after four courses. Computed tomography indicated a partial response, and operability was feasible. Therefore, thoracoscopic left upper lobectomy was performed after six courses of pembrolizumab, and histological assessment of the treatment effect was determined to be Ef 3, a complete response. The postoperative course was uneventful and he was discharged on the third postoperative day. We encountered a case that could be surgically treated after pembrolizumab administration. This treatment was safe and effective for advanced lung cancer.

The outcome and risk factors for recurrence and extended hospitalization of secondary spontaneous pneumothorax.

PURPOSE: Secondary spontaneous pneumothorax (SSP) is difficult to treat by itself and due to its association with serious underlying diseases. It has a high rate of recurrence and often requires extended hospitalization. Therefore, we evaluated the outcome and risk factors associated with recurrence and extended hospitalization. METHODS: We retrospectively examined 61 patients with SSP, and evaluated the patients' characteristics, underlying diseases, introduction of home oxygen therapy, Brinkman index, and X-ray imaging findings to determine the risk factors for recurrence and extended hospitalization. RESULTS: There were 28 patients (46.0%) with chronic obstructive pulmonary disease, 8 (13.1%) with interstitial pneumonia, 16 (26.2%) with massive emphysema, and 9 (14.8%) with other diseases. Adhesion and mediastinal shift visualized by X-ray imaging were observed in 37 (37.9%) and 25 patients (40.1%), respectively. Recurrence occurred in 25 patients (40.9%) and the average hospitalization duration was 14.5 days (±11.2). A multivariate analysis showed that adhesion on X-ray imaging was a significant risk factor for recurrence (odds ratio 4.90, 95% confidence interval 1.38-21.44) and mediastinal shift on X-ray imaging was a significant risk factor for extended hospitalization (odds ratio 6.05, 95% confidence interval 1.44-31.06). CONCLUSIONS: Findings from X-ray imaging, and not underlying diseases, are risk factors for recurrence and extended hospitalization.

Novel method for rapid fluorescence in-situ hybridization of ALK rearrangement using non-contact alternating current electric field mixing.

Echinoderm microtubule-associated protein-like 4 gene and anaplastic lymphoma kinase gene (EML4-ALK) rearrangement is a key driver mutation in non-small cell lung cancer (NSCLC). Although Break-Apart ALK fluorescence in situ hybridization (FISH) is a reliable diagnostic method for detecting ALK gene rearrangement, it is too costly and time-consuming for use as a routine screening test. Our aim was to evaluate the clinical utility of a novel rapid FISH (RaFISH) method developed to facilitate hybridization. RaFISH takes advantage of the non-contact mixing effect of an alternating current (AC) electric field. Eighty-five specimens were used from patients diagnosed with NSCLC identified immunohistochemically as ALK 0, (1/2+) or (3+). With RaFISH, the ALK test was completed within 4.5 h, as compared to 20 h needed for the standard FISH. Although RaFISH produced results more promptly, the staining and accuracy of the ALK evaluation with RaFISH was equal to the standard. We found 97.6% agreement between FISH and RaFISH based on the status of the ALK signals. These results suggest RaFISH could be used as a clinical tool to promptly determine ALK status.

[Mediastinal Pancreatic Pseudocyst with Pancreatic Pleural Effusion].

A 72-year-old man with chronic alcohol related pancreatitis was admitted for dyspnea and pain at the upper body. Chest X-ray showed right massive pleural effusion. Chest and abdominal contrast enhanced thin slice computed tomography revealed the route from the pancreatic head reaching the right thoracic cavity via the esophagus hiatus and the communication between the cystic lesion and main pancreatic duct. We drained the pleural effusion that showed abnormally high amylase activity. We diagnosed his illness as mediastinal pancreatic pseudocyst with pancreatic pleural effusion. Endoscopic Nasopancreatic Drainage catheter was placed in the main pancreatic duct, and the pleural effusion disappeared.

Gender differences in the correlation between prognosis and postoperative weight loss in patients with non-small cell lung cancer.

OBJECTIVES: The aim of this study was to investigate gender differences in the relationship between preoperative body mass index (BMI), postoperative body weight change and prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: Two hundred and sixty-three patients with NSCLC were enrolled in this study. Preoperative BMI was categorized based on WHO definition as follows: underweight (BMI <18.5): 21 patients (8.0%), normal (18.5 ≦ BMI <25): 179 patients (68%), overweight and obese (BMI ≧25): 63 patients (24%). Several factors such as age, sex, cancer stage, body weight change and BMI were recorded and correlated to the postoperative overall survival (OS). RESULTS: For male patients, those in the low-BMI group had the worst prognosis (P < 0.05) whereas female patients with low BMI did not. Male patients with low BMI had statistically significant poorer prognosis compared to corresponding female patients (P < 0.05). Male patients with more than 5% body weight loss within 1 year after operation when compared to preoperative body weight had poorer prognosis than those with less than 5% body weight loss (P < 0.001). Furthermore, these male patients had statistically significant worse prognosis than the corresponding female patients (P < 0.05). In multivariable analysis, gender, more than 5% of body weight loss compared to preoperative body weight, and pathological stage were independent prognostic factors in NSCLC. CONCLUSIONS: This study illustrates significant gender differences in the relationship between prognosis and BMI or body weight change in patients with postoperative NSCLC.

New PET/CT criterion for nodal staging in non-small cell lung cancer: measurement of the ratio of section area of standard uptake values ≥2.5/lymph node section area.

BACKGROUND: The aim of the present study was to use surgical and histological results to develop a simple noninvasive technique for improving nodal staging using preoperative PET/CT in patients with resectable non-small cell lung cancer (NSCLC). METHODS: Preoperative PET/CT findings (163 patients) and pathological diagnoses after surgical resection were evaluated. Using PET/CT images, lymph node section area (SA), the maximum standardized uptake value (SUVmax), SA of SUV ≥2.5 and ≥3.0 were drawn freehand and measured using caliper software. Receiver operating characteristic (ROC) curves were then used to analyze those data. RESULTS: Based on ROC analyses, the cut-off values for SA of SUV ≥2.5, SA of SUV ≥3.0, SUV ≥2.5 SA/node SA and SUV ≥3.0 SA/node SA for diagnosis of lymph node metastasis were 200 mm2, 30 mm2, 1.0 and 0.4. SUV ≥2.5 SA/node SA ≥1.0 had the highest negative predictive value, and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of nodal staging were 61.1, 73.4, 36.7, 88.2 and 70.9%. CONCLUSIONS: When diagnosing nodal staging based a lymph node SUV ≥2.5 SA/node SA ratio of ≥1.0, it can be an effective criterion for use to determine surgical indications.

Thymic carcinoma with myasthenia gravis: Two case reports.

INTRODUCTION: Myasthenia gravis (MG) has been reported to correlate with earlier-stage thymoma, and theoretically does not accompany thymic carcinoma. However, we encountered two cases of thymic carcinoma with MG. PRESENTATION OF CASES: Case 1 involved a 54-year-old man who had been diagnosed with MG based on symptoms and detection of anti-acetylcholine receptor antibody (ARAB). Computed tomography (CT) revealed an anterior mediastinal tumor 30mm in diameter. Prednisolone (PSL) and tacrolimus were administered without surgery at that time. Six years after diagnosis of MG, he was admitted to our hospital and underwent extended thymectomy. Pathological examination revealed type B2-B3 thymoma according to World Health Organization criteria, comprising 80% of the tumor with small cell carcinoma as 20%. Case 2 involved a 51-year-old woman. She had been diagnosed with MG based on eyelid ptosis and detection of ARAB. Ten years after diagnosis of MG, diaphragm elevation was detected on chest X-ray. CT revealed an anterior mediastinal tumor, 47mm in diameter. We suspected tumor invasion to the right phrenic nerve, right atrium, and superior vena cava. We therefore performed extended thymectomy after preoperative radiotherapy (40Gy). Pathological examination revealed squamous cell carcinoma. DISCUSSION: Most cases of thymic carcinomas appear to arise de novo, but appearance in thymomas has been described. In both our cases, MG was treated with pharmacotherapy alone without extended thymectomy, and thymic carcinoma was considered to have developed from the thymoma during long-term follow-up. CONCLUSION: Thymic carcinoma can accompany MG.

Novel method for rapid in-situ hybridization of HER2 using non-contact alternating-current electric-field mixing.

Human epidermal growth factor receptor 2 (HER2)-targeted agents are an effective approach to treating HER2-positive breast cancer patients. However, the lack of survival benefit in HER2-negative patients as well as the toxic effects and high cost of the drugs highlight the need for accurate and prompt assessment of HER2 status. Our aim was to evaluate the clinical utility of a novel rapid dual in-situ hybridization (RISH) method developed to facilitate hybridization. The method takes advantage of the non-contact mixing effect of an alternating current (AC) electric field. One hundred sixty-three specimens were used from patients diagnosed with primary breast cancers identified immunohistochemically as HER2 0/1(+), (2+) or (3+). The specimens were all tested using conventional dual in-situ hybridization (DISH), DISH with an automated slide stainer, and RISH. With RISH the HER2 test was completed within 6 h, as compared to 20-22 h needed for the standard protocol. Although RISH produced results more promptly using smaller amounts of labeled antibody, the staining and accuracy of HER2 status evaluation with RISH was equal to or greater than with DISH. These results suggest RISH could be used as a clinical tool to promptly determine HER2 status.

Development of a New Magnetometer for Sentinel Lymph Node Mapping Designed for Video-Assisted Thoracic Surgery in Non-Small Cell Lung Cancer.

BACKGROUND: We previously developed a method for sentinel lymph node (SLN) mapping in non-small cell lung cancer (NSCLC), based on the magnetic force produced by a magnetite tracer already approved for use as a contrast material for magnetic resonance imaging. However, it is difficult to use that technique with video-assisted thoracic surgery (VATS) because the sensing element of the magnetometer is large and thick. The purpose of the present study was to develop a smaller, thinner VATS-compatible magnetometer. METHODS: The tracer employed was Ferucarbotran, a colloidal solution of superparamagnetic iron oxide coated with carbodextran. Fifteen patients with clinical stage I NSCLC were enrolled, and each received 1.6 mL of Ferucarbotran, injected intraoperatively at 5 points around the tumor. The magnetic force within the sampling lymph nodes was measured using the new VATS-compatible magnetometer. RESULTS: SLNs were detected in 11 (73.3%) of the 15 patients using the VATS-compatible magnetometer. The average number of SLNs identified per patient was 1.8 (range 0-4). No complications related to the SLN detection method were observed. CONCLUSIONS: The new VATS-compatible magnetometer appears to have substantial advantages over techniques using a radioisotope and our earlier magnetometer, as it can be inserted through the small VATS port site.

Strong expression of cyclin B2 mRNA correlates with a poor prognosis in patients with non-small cell lung cancer.

Cyclin family proteins act in association with cyclin-dependent kinases (CDK) at cell cycle checkpoints to regulate the eukaryotic cell cycle. CyclinB2 contributes to G2/M transition by activating CDK1 kinase, and cyclin B2 inhibition induces cell cycle arrest. CyclinB2 is overexpressed in various human tumors, though the relationship between cyclin B2 expression and the clinicopathological characteristics of lung cancer and patient prognosis is not well understood. In the present study, therefore, we investigated the relationship between cyclin B2 mRNA expression and the prognosis of patients with non-small cell lung cancer (NSCLC). We used semiquantitative real-time reverse transcription polymerase chain reaction to assess the expression of cyclin B2 mRNA in tumor samples from 79 patients with NSCLC. We then correlated the cyclin B2 mRNA levels with clinicopathological factors. We also used immunohistochemical staining to determine the localization of expressed cyclin B2. The 5-year overall survival rates among patients with adenocarcinoma of lung expressing lower levels of cyclin B2 mRNA were significantly better than the corresponding rates among patients expressing higher levels (p = 0.004). Multivariate Cox proportional hazard analyses revealed that gender ((hazard ratio (HR), 9.81; p = 0.044)), n2 (HR, 146.26; p ≤ 0.001), and cyclin B2 mRNA high (HR, 7.21; p = 0.021) were independent factors affecting the 5-year overall survival rates. However, there was no significance in the 5-year overall survival rates among the patients with squamous cell carcinoma between expressing lower and higher level of cyclin B2 mRNA. Stronger expression of cyclin B2 mRNA in tumor cells is an independent predictor of a poor prognosis in patients with adenocarcinoma of lung.