Prognostic Value of CXCL12 in Non-Small Cell Lung Cancer Patients Undergoing Tumor Resection.

Adjuvant chemotherapy is commonly indicated in lung cancer patients undergoing surgical therapy because tumor recurrence is frequent. A biomarker that can predict tumor recurrence in the postoperative period is currently unavailable. CXCR4 receptor and its ligand CXCL12 play important roles in metastasis. This study investigated the value of tumor CXCL12 expression to predict prognosis and indicate adjuvant chemotherapy in non-small cell lung cancer patients. This study enrolled 82 non-small cell lung cancer patients. The expression of CXCL12 was evaluated by immunohistochemistry. The degree of CXCL12 expression was assessed using the Allred score system. Among all subjects, the progression-free survival and overall survival were significantly prolonged in cancer patients with low tumor expression of CXCL12 compared to patients with high tumor expression. Multivariate analysis showed that the increased level of CXCL12 is a significant predictor of progression-free survival and overall survival in NSCLC patients. Among subjects with high tumor CXCL12 expression, progression-free survival and overall survival were significantly improved in patients treated with adjuvant chemotherapy compared to untreated patients. These results suggest the potential value of tumor CXCL12 expression as a marker to predict prognosis and to indicate adjuvant chemotherapy after surgical tumor resection in non-small cell lung cancer patients.

Comparison of the efficacy of novel two covering methods for spontaneous pneumothorax: a multi-institutional study.

OBJECTIVES: The postoperative recurrence rate after thoracoscopic bullectomy for primary spontaneous pneumothorax (PSP) is not satisfactory. This retrospective study was conducted to elucidate an effective technique for improving the postoperative recurrence rate. METHODS: The present study included 373 patients who underwent thoracoscopic bullectomy for PSP at three hospitals from January 2013 to May 2020. We compared the recurrence rate according to two methods that were used to cover the staple line after thoracoscopic bullectomy. Group A (146 patients) was treated with an absorbable polyglycolic acid (PGA) sheet plus fibrin glue and oxidised regenerated cellulose (ORC). Group B (227 patients) was treated with ORC alone. RESULTS: There was no significant difference in preoperative characteristics of the patients. The postoperative recurrence rate of pneumothorax was 3.4% (5/146) in Group A and 17.2% (39/227) in Group B, respectively. Among 23 patients (Group A, n=3 and Group B, n=20) who received reoperation for recurrent pneumothorax, the site of recurrence was around the stapler line of the first operation in 1 of 5 (20%) patients in Group A and 28 of 39 (71.8%) patients in Group B. The 1-year recurrence-free rate was 97.4% (median follow-up period, 73 days (range, 2-3952 days)) in Group A and 80.9% (median follow-up period, 71 days (range 2-2648 days)) in Group B. CONCLUSIONS: Coverage with a PGA sheet may prevent the postoperative recurrence of PSP. A large-scale prospective randomised study should be conducted to clarify the most effective treatment for PSP.

Extended Bronchoplasty Anastomosed between the Left Main and the Superior Segmental Bronchi for Locally Advanced Left Upper Lobe Lung Cancer with Invasion of the Basal Segment.

We report a case of extended bronchoplasty in which anastomosis between the left main and the superior segmental bronchi with resection of the left upper lobe and basal segment was required to avoid pneumonectomy for locally advanced lung cancer. The main tumor located at the left upper lobe invaded the basal segment, and involved both the basal pulmonary artery and left secondary carina. Regarding anastomosis, the bronchi were cut in a deep wedge shape and a wall flap was made by part of the lower lobar bronchus. The patient's postoperative course was uneventful and he has been alive without recurrence for more than 3 years after surgery.

A simple and reliable method to preoperatively detect a common trunk of the left pulmonary vein.

BACKGROUND: It is difficult to detect a common trunk of the left pulmonary vein (PV) preoperatively, which may cause intraoperative accidental complications. The purpose of this study is to establish a simple and reliable method of detecting a common trunk in preoperative computed tomography (CT) images. METHODS: A total of 428 patients who underwent thin-section CT preoperatively for left lung cancer at 4 institutions were reviewed. The characteristic findings of a common trunk in the axial view were considered by confirming the preoperative CT findings of cases that had been verified to have a common trunk based on intraoperative findings. The CT images were reviewed independently by two evaluators. RESULTS: We found that the distance between the mediastinal side of the left lower bronchus and the junction of two left PVs was extremely short in the cases with a common trunk in the axial view. In a typical case, the axial section of the bronchus is close to the junction. Of the 416 patients that were evaluable among the 428 total patients, 26 (6.3%) were diagnosed as having a common trunk by both evaluators, and the diagnosis was coincident in 413 patients (99.2%). We were able to evaluate the surgical videos of 16 of the 26 patients, and a common trunk was confirmed in 15 patients (94%). CONCLUSIONS: We established a simple and reliable method of detecting a common trunk of the left PV in the axial view on chest CT that was routinely performed prior to lung cancer surgery.

Three-year Survival Rate after Radiofrequency Ablation for Surgically Resectable Colorectal Lung Metastases: A Prospective Multicenter Study.

Background Although radiofrequency ablation (RFA) is widely performed for the treatment of colorectal cancer (CRC) lung metastases, its efficacy for candidates with surgically resectable disease is unclear. Purpose To evaluate the prognosis after RFA in participants with resectable CRC lung metastases. Materials and Methods For this prospective multicenter study (ClinicalTrials.gov identifier: NCT00776399), participants with five or fewer surgically resectable lung metastases measuring 3 cm or less were included. Participants with CRC and a total of 100 lung metastases measuring 0.4-2.8 cm (mean, 1.0 cm ± 0.5) were chosen and treated with 88 sessions of RFA from January 2008 to April 2014. The primary end point was the 3-year overall survival (OS) rate, with an expected rate of 55%. The local tumor progression rate and safety were evaluated as secondary end points. The OS rates were generated by using the Kaplan-Meier method. Log-rank tests and Cox proportional regression models were used to identify the prognostic factors by means of univariable and multivariable analyses. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. Results Seventy participants with CRC (mean age, 66 years ± 10; 49 men) were evaluated. The 3-year OS rate was 84% (59 of 70 participants; 95% confidence interval [CI]: 76%, 93%). In multivariable analysis, factors associated with worse OS included rectal rather than colon location (hazard ratio [HR] = 7.7; 95% CI: 2.6, 22.6; P < .001), positive carcinoembryonic antigen (HR = 5.8; 95% CI: 2.0, 16.9; P = .001), and absence of previous chemotherapy (HR = 9.8; 95% CI: 2.5, 38.0; P < .001). Local tumor progression was found in six of the 70 participants (9%). A grade 5 adverse event was seen in one of the 88 RFA sessions (1%), and grade 2 adverse events were seen in 18 (20%). Conclusion Lung radiofrequency ablation provided a favorable 3-year overall survival rate of 84% for resectable colorectal lung metastases measuring 3 cm or smaller. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Gemmete in this issue.

Talc pleurodesis for secondary pneumothorax in elderly patients with persistent air leak.

BACKGROUND: We herein report the usefulness of two types of talc pleurodesis for secondary pneumothorax of elderly patients with persistent air leak who have severe pulmonary emphysema. METHODS: We assessed 17 elderly patients with persistent air leak who received talc pleurodesis for secondary pneumothorax from April 2013 to March 2017. Thoracoscopic talc poudrage (TTP) (n=11) was performed in patients whose general condition was thought to sufficiently stable to tolerate for general anesthesia. Talc slurry pleurodesis (TSP) (n=6) via a chest tube was performed in patients whose general condition was thought to be insufficiently stable to tolerate general anesthesia. RESULTS: The median drainage period after pleurodesis was 6 days in patients who received TTP and 12 days in patients who received TSP. Complications associated with talc pleurodesis included atrial fibrillation (n=1) in the thoracoscopic poudrage group, while the slurry pleurodesis group showed chest pain (n=2), asthmatic attack (n=1), and pneumonia (n=1). All patients who received thoracoscopic poudrage were able to leave the hospital after removal of the chest tube. Five of the six patients who received slurry pleurodesis were able to leave the hospital, but one of them died of acute exacerbation of interstitial pneumonia (IP) on the 45th day after pleurodesis. The success rate was 94% (16/17). There were no cases of recurrence during the observation period. CONCLUSIONS: TTP was deemed likely to be safe and effective for patients able to tolerate general anesthesia. In patients with IP, especially those treated with steroids, the indication of talc pleurodesis should be cautiously considered.

Ciliated muconodular papillary tumor of the lung: A report of five cases.

Ciliated muconodular papillary tumor (CMPT) of the lung is a newly defined and extremely rare tumor characterized by a papillary growth pattern, consisting of ciliated columnar cells, mucous cells, and basal cells with abundant mucin production. Tumor definitions and clinicopathological features continue to be debated. Herein, we report five surgical cases of CMPT to characterize its radiographic, gross, and microscopic features. The five cases involved three male patients aged 80, 67, and 66 years, and two female patients aged 73 and 70 years. Three cases were discovered during health care screenings, and two cases were found during follow-up for another synchronous cancer. Histopathological examination revealed that the tumor tissue was composed of ciliated columnar cells, mucous cells, and basal cells with abundant mucin production. Neither nuclear atypia nor mitotic figures were observed. All patients had good prognoses. The benign histological features and clinical courses in these five cases suggest that CMPT is an independent and benign tumor of the lung.

Successful treatment of mucoepidermoid carcinoma in the left main bronchus.

Here, we report the successful treatment of a 40-year-old man with mucoepidermoid carcinoma that originated in the proximal end of the left main bronchus close to the carina. He underwent wide and deep airway wedge resection, including the distal trachea and part of the carina via left postero-lateral thoracotomy. He has demonstrated neither anatomic complications nor disease recurrence 2 years after the operation.

Radiofrequency ablation for ground-glass opacity-dominant lung adenocarcinoma.

PURPOSE: To evaluate retrospectively the clinical utility of lung radiofrequency (RF) ablation for the treatment of ground-glass opacity (GGO)-dominant lung adenocarcinoma. MATERIALS AND METHODS: From August 2004 through May 2012, 33 consecutive patients (14 men and 19 women; mean age, 71.1 y; age range, 46-84 y) with 42 lung tumors having ≥ 50% GGO component received lung RF ablation. The mean maximum tumor diameter was 1.6 cm ± 0.9 (range, 0.7-4.0 cm). Feasibility, safety, local tumor progression, and survival were evaluated. RESULTS: For the 42 RF sessions, after RF electrodes were placed in each target tumor, planned ablation protocols were completed in all sessions (100%; 42 of 42). No deaths related to the RF procedure occurred. Major and minor complication rates were 4.8% and 23.8%, respectively. Local tumor progression developed in 6 tumors (14.3%; 6 of 42) during a mean follow-up of 42 months ± 23 (range, 5-92 mo). Four of six tumors with local progression were controlled by repeated RF ablation. No evidence of disease was achieved in 31 of 33 patients (93.9%) at the end of the follow-up period. All but one patient (who died of brain hemorrhage) are alive today. Overall and cancer-specific survival rates were 100% and 100% at 1 year, 96.4% (95% confidence interval [CI], 77.5%-99.5%) and 100% at 3 years, and 96.4% (95% CI, 77.5%-99.5%) and 100% at 5 years, respectively. CONCLUSIONS: Lung RF ablation is a feasible, safe, and useful therapeutic option to control GGO-dominant lung adenocarcinoma.

Adverse events of pulmonary vascular stapling in thoracic surgery.

OBJECTIVES: The use of staplers for thoracic surgery has been widely accepted and regarded as a safe procedure. However, adverse events (AEs) of stapling are occasionally experienced. The aim of this retrospective study was to analyse the AEs of stapling in pulmonary vascular surgery. METHODS: A retrospective multi-institutional review was conducted by the 29 institutions of the Central Japan Lung Cancer Surgery Study Group. All staplings of the pulmonary artery (PA) and vein in thoracic surgery were reviewed during the research period. RESULTS: Stapling of the PA and vein was performed 3393 times. The total number of AEs related to stapling was nine (0.27%). Eight events occurred intraoperatively and one occurred immediately after the operation. Intraoperative AE occurred more frequently than postoperative AE. AE in the PA occurred more frequently than in the pulmonary vein. The intraoperative AEs were oozing (n=3), stapling failure (n=2), laceration of the peripheral vasculature at compression (n=2) and technical injury of the vasculature at insertion (n=1). The causes of AEs were reported to be tissue fragility (n=3), stapler rocking during stapling (n=2), stapler-tissue thickness mismatch (n=2) and technical failure (n=1). The only postoperative AE was staple line rupture of the PV stump. No relationship was seen between the incidence of AE and cartridge colours, compression types of staplers or numbers of staple lines. CONCLUSIONS: Generally, stapling of the pulmonary vasculatures in recent thoracic surgery has been safe. Furthermore, the knowledge of the possible risks of pulmonary vascular stapling may help to decrease the AEs of stapling.

[Incidence of string-like adhesion between thoracic wall and bullae observed during video-assisted thoracic surgery( VATS) for spontaneous pneumothorax].

It is not rare that string-like adhesion between lung apex and chest wall is observed during videoassisted thoracic surgery (VATS) for spontaneous pneumothorax. This adhesion may cause hemothorax which requires emergency operation, although the precise incidence of such cases is uncertain. We analyzed consecutive 120 spontaneous pneumothorax cases underwent VATS at Suzuka General Hospital from January 2005 to September 2008. Twenty-one out of 120 (17.5%) were such cases receiving partial resection of the lung including the adhesion after dividing it. Pathological study revealed the bullae close to the adhesion in all cases, suggesting that these adhesion caused after possible former pneumothorax. Thus, 21 cases might be recurrent pneumothorax. Even in clinically 1st onset pneumothorax, those cases may be good indication for VATS.

[A case of metastatic pulmonary cancer from renal cell carcinoma masquerading as pulmonary vein varix].

A 66-year-old woman underwent nephrectomy to treat renal cell carcinoma 5 years previously. Enhanced CT to locate the tumor revealed a lesion very close to the right upper pulmonary vein. Six months later, the nodule grew to 14mm in maximum dimension and it seemed to be a varix of the right upper pulmonary vein on 3D-CT. However, pulmonary artery angiography (PAG) denied this possibility. PET-CT revealed the nodule to be positive for FDG uptake (maxSUV 2.7 in the early phase and 2.2 in the late phase), suggesting that it contained solid tissue with malignant characteristics. Eventually, right upper lobectomy was performed. The nodule was a metastatic renal cell carcinoma with extremely abundant vascular components. This conspicuous feature of the tumor appeared to mimic a pulmonary vein varix on enhanced CT scan and 3D angiogram.

Artificial pneumomediastinum facilitates thoracoscopic surgery in anterior mediastinum.

A 67-year-old woman underwent a thoracoscopic resection of a large anterior mediastinal cyst. Before surgery, artificial pneumomediastinum was performed with a retrosternal technique. Injection of 400 ml of air from the sternal notch caused emphysema throughout the mediastinum. In those areas, dissection of loose connective tissue was mostly accomplished by the injected air, which formed an air layer around the cyst. On the other hand, emphysema was not apparent in the areas around the left innominate and thymic veins. Artificial pneumomediastinum may be useful as a supplementary technique in a thoracoscopic surgery setting.

ACTH-secreting thymic carcinoid associated with multiple endocrine neoplasia type 1.

Thymic carcinoids are classified into three categories: (1) nonsecretory tumors, (2) hormonal secretory tumors, and (3) tumors associated with multiple endocrine neoplasia type 1. We report a rare case with adrenocorticotropic hormone secreting thymic carcinoid with multiple endocrine neoplasia type 1. Radiologic examination showed an anterior mediastinal mass and a parathyroid tumor. Blood analysis revealed high levels of parathyroid hormone and adrenocorticotropic hormone. Urine cortisol and 17-hydroxycorticoids levels were also elevated. Extended thymectomy was performed. Subsequently adjuvant radiation therapy and parathyroid tumor resection were performed. A germline mutation of exon 7 in the multiple endocrine neoplasia type 1 gene was detected and a somatic mutation of exon 9 was demonstrated in the thymic tumor.

Epidermal growth factor receptor gene mutation in non-small cell lung cancer using highly sensitive and fast TaqMan PCR assay.

Epidermal growth factor receptor (EGFR) gene mutations have been found in a subset of non-small cell lung cancer (NSCLC) with good clinical response to gefitinib therapy. A quick and sensitive method with large throughput is required to utilize the information to determine whether the molecular targeted therapy should be applied for the particular NSCLC patients. Using probes for the 13 different mutations including 11 that have already been reported, we have genotyped the EGFR mutation status in 94 NSCLC patients using the TaqMan PCR assay. We have also genotyped the EGFR mutations status in additional 182 NSCLC patients, as well as 63 gastric, 95 esophagus and 70 colon carcinoma patients. In 94 NSCLC samples, the result of the TaqMan PCR assay perfectly matched with that of the sequencing excluding one patient. In one sample in which no EGFR mutation was detected by direct sequencing, the TaqMan PCR assay detected a mutation. This patient was a gefitinib responder. In a serial dilution study, the assay could detect a mutant sample diluted in 1/10 with a wild-type sample. Of 182 NSCLC samples, 46 mutations were detected. EGFR mutation was significantly correlated with gender, smoking status, pathological subtypes, and differentiation of lung cancers. There was no mutation detected by the TaqMan PCR assay in gastric, esophagus and colon carcinomas. TaqMan PCR assay is a rapid and sensitive method of detection of EGFR mutations with high throughput, and may be useful to determine whether gefitinib should be offered for the treatment of NSCLC patients. The TaqMan PCR assay can offer us a complementary and confirmative test.

Endoscopic thoracic sympathectomy for palmar hyperhidrosis: efficacy of T2 and T3 ganglion resection.

BACKGROUND: Endoscopic thoracic sympathectomy has been considered an effective treatment for palmar hyperhidrosis. However, the extent of resection has not been determined in terms of efficacy and complications. We compared the efficacy and complications of 2-ganglion and single-ganglion resection in patients with palmar hyperhidrosis. METHODS: From 1995 to 2000, 75 patients underwent resection of thoracic ganglion T2 and T3. From 2000 to 2003, 67 patients underwent resection of only the T2 ganglion. Eighty of the 142 patients (56%) answered a detailed questionnaire, the results of which were analyzed. RESULTS: Gender, age, family history, and distribution of sweating were similar in both groups. Recurrence rates 1 and 2 years after endoscopic thoracic ganglionectomy were between 0% and 3% in T2 and T3 resection, and between 15% and 19% in T2 resection only. In the combined T2 and T3 resection group, 100% of patients noticed compensatory sweating; in T2 resection, 90% of patients noticed compensatory sweating. As for rates of satisfaction, T2 and T3 resection was superior to T2 resection. CONCLUSIONS: High recurrence rates of palmar hyperhidrosis after single-ganglion resection are reported in the present study. Two-ganglion resection is a superior surgical method to prevent recurrence of palmar hyperhidrosis.

EGFR Mutation status in Japanese lung cancer patients: genotyping analysis using LightCycler.

PURPOSE: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in approximately 25% of Japanese lung cancer patients. These EGFR mutations are reported to be correlated with clinical response to gefitinib therapy. However, DNA sequencing using the PCR methods described to date is time-consuming and requires significant quantities of DNA; thus, this existing approach is not suitable for a routine pretherapeutic screening program. EXPERIMENTAL DESIGN: We have genotyped EGFR mutation status in Japanese lung cancer patients, including 102 surgically treated lung cancer cases from Nagoya City University Hospital and 16 gefitinib-treated lung cancer cases from Kinki-chuo Chest Medical Center. The presence or absence of three common EGFR mutations were analyzed by real-time quantitative PCR with mutation-specific sensor and anchor probes. RESULTS: In exon 21, EGFR mutations (CTG --> CGG; L858R) were found from 8 of 102 patients from Nagoya and 1 of 16 from Kinki. We also detected the deletion mutations in exon 19 from 7 of 102 patients from Nagoya (all were deletion type 1a) and 4 of 16 patients from Kinki (one was type 1a and three were type 1b). In exon 18, one example of G719S mutation was found from both Nagoya and Kinki. The L858R mutation was significantly correlated with gender (women versus men, P < 0.0001), Brinkman index (600 < or = versus 600, P = 0.001), pathologic subtypes (adenocarcinoma versus nonadenocarcinoma, P = 0.007), and differentiation status of the lung cancers (well versus moderately or poorly, P = 0.0439), whereas the deletion mutants were not. EGFR gene status, including the type of EGFR somatic mutation, was correlated with sensitivity to gefitinib therapy. For example, some of our gefitinib-responsive patients had L858R or deletion type 1a mutations. On the other hand, one of our gefitinib-resistant patients had a G719S mutation. CONCLUSIONS: Using the LightCycler PCR assay, the EGFR L858R mutation status might correlate with gender, pathologic subtypes, and gefitinib sensitivity of lung cancers. However, further genotyping studies are needed to confirm the mechanisms of EGFR mutations for the sensitivity or resistance of gefitinib therapy for the lung cancer.

Histone deacetylase 1 mRNA expression in lung cancer.

Histone deacetylases (HDACs) play a crucial role in tumorigenesis, however, the expression status of HDACs in lung cancer tissues has not been reported. We have investigated that HIDAC 1 mRNA levels and other clinico-pathological data, including MTA 1 mRNA expression in lung cancer. The study included 102 lung cancer cases. The HDAC1 mRNA levels were quantified by real time reverse transcription-polymerase chain reaction (RT-PCR) using LightCycler (Roche Molecular Biochemicals, Mannheim, Germany). The HDAC1/GAPDH mRNA levels were not significantly different in tumor tissues from lung cancer (30.654 +/- 33.047) and adjacent non-malignant lung tissues (18.953 +/- 56.176 , P = 0.1827). No significant difference in HDAC1/GAPDH mRNA levels was found among age, gender, and lymph node metastasis. The HDAC1/GAPDH mRNA levels were significantly higher in stage III or IV lung cancer (50.929 +/- 120.433) than in stage I lung cancer (11.430 +/- 25.611, P = 0.0472). HDAC1/GAPDH mRNA levels were significantly higher in T3 or T4 lung carcinoma (54.326 +/- 127.018) than in T1 or T2 lung cancers (14.790 +/- 48.670, P = 0.1601). HDAC1/GAPDH mRNA levels were correlated with MTA1/GAPDH mRNA levels (y = 0.0106x + 2.5827 , P = 0.0352 ). HDAC1/GAPDH mRNA levels were also correlated with HDAC1 protein (P = 0.0484) expression by immunohistochemistry. Using the LightCycler RT-PCR assay, the HDAC1 gene expression might correlate with progression of lung cancers. However, further studies are needed to confirm the impact of HDAC1 for the molecular target of the lung cancer.

Decreased Hrad6B expression in lung cancer.

Human homologues of yeast Rad 6 (Hrad6B) encode ubiquitin-conjugating enzymes and complement the DNA repair and UV mutagenesis defects of Saccharomyces cerevisiae rad6 mutant. There is a larger subgroup with reduced DNA repair capacity that is likely to be at increased cancer risk. The authors investigated Hrad6B expression in lung cancer. An attempt was made to determine the influence of Hrad6B expression on clinicopathological features for patients with lung cancer who had undergone surgery. Expression of Hrad6B messenger RNA was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 110 lung carcinomas and adjacent histological non-malignant lung samples from patients for whom follow-up data were available using LightCycler. The Hrad6B/glyceraldehydes-3-phosphate dehydrogenase (GAPDH) mRNA expression was significantly decreased in the lung cancer tissue (4.078+/-5.674) as compared with the non-malignant lung tissue (10.495+/-12.976, p<0.001). There was no relationship between Hrad6B/GAPDH expression and age, clinical stages, T-status, N-status, and pathological subtypes in lung cancer tissues. Hrad6B/GAPDH mRNA levels in males (3.521+/-4.280) and in females (6.420+/-8.167) were significantly different (p=0.0443) in lung cancer tissues, but not in non-malignant lung tissues. Heavy smokers had a slight non-significant tendency (p=0.0857) towards lower Hrad6B/GAPDH mRNA levels (3.453+/-4.743) in their lung cancer tissues as compared with light or non-smokers. Thus decreased Hrad6B mRNA expression might be a biomarker for decreased DNA repair capacity and the dysfunction of Hrad6B might play a role in the tobacco-related oncogenesis of lung cancer.