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Fibroblast growth factor receptor (FGFR)-signaling in lung squamous cell carcinoma (LSCC) is associated with cancer aggressiveness and poor prognosis. Small GTPase RAB11A regulates the recycling of membrane proteins such as FGFR. This study evaluated the potential of RAB11A as a new therapeutic target for LSCC through its regulation of FGFR-signaling.Immunohistochemical analysis of 84 LSCC samples was performed to determine the correlation between RAB11A expression, clinicopathologic features, and prognosis. Alterations in FGFR-signaling were assessed in RAB11A-suppressed and RAB11A-overexpressed LSCC cells both in vitro and in vivo.The study identified RAB11A as a strong predictor of poor prognosis in the LSCC cohort. Cell proliferation and invasion were promoted and inhibited respectively in RAB11A-overexpressed and RAB11A -suppressed LSCC cells. In RAB11A-overexpressed and RAB11A-suppressed LSCC cells, FGFR-signaling was respectively up- and downregulated. The viability of the cells treated with nintedanib and lenvatinib was greater in RAB11A-overexpressing cells than in control cells. The in vivo tumor growth and micro-vessel density of RAB11A-overexpressing tumors were significantly higher than in the control cells.As a potentially valuable prognostic marker, RAB11A is a promising therapeutic target for LSCC. Evaluation of RAB11A may be useful for identification of LSCC in patients whose cancer is refractory to FGFR inhibitors.

Lung segmentectomy is an option for the treatment of noninvasive or minimally invasive lung cancer. For tumors located in the left upper division (LUD), LUD trisegmentectomy (SWe compared the surgical outcomes and frequency of postoperative complications of LUD trisegmentectomy (simple group) with those of complex segmentectomy (other than LUD trisegmentectomy; complex group) for pulmonary lesions using three-dimensional computed tomography between 2010 and 2021.In total, 118 patients were included: 65 in the simple group and 53 in the complex group (SComplex segmentectomy can be performed safely under the guidance of three-dimensional CT. Complex segmentectomy itself is not a risk factor for postoperative complications when the intersegmental planes are sufficiently recognized and accurately cut.

Background Resection of lung cancer with chest wall involvement is an invasive procedure. Case presentation We report a case of pulmonary adenocarcinoma with chest wall involvement that was resected through video-assisted thoracoscopic segmentectomy and combined en bloc resection of the chest wall (2nd to 4th ribs). Surgical stress was decreased by reducing the extent of lung parenchymal resection and applying a video-assisted technique with an additional posterior paravertebral incision. Conclusion A thoracoscopic surgical approach involving incisions in areas requiring resection of the proximal, lateral, and posterior sides of the involved ribs can be applied to tumors invading the chest wall.

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., High expression of chemosensitive markers such as Topo‐II and TS may be responsible for the poor prognosis of LCNEC patients. Furthermore, VEGFR2 expression is negatively correlated with antitumor immune response and may not be just a chemosensitive marker. The expression of chemosensitive markers is an important prognostic factor for LCNEC and may be a biomarker of resistance to overall treatment of lung cancer, such as immune checkpoint inhibitors.

Three-dimensional (3D) imaging is an essential tool for performing an accurate segmentectomy. However, data acquired from contrast-enhanced computed tomography (CT) are considered necessary when reconstructing 3D pulmonary vascular images. Therefore, 3D images are currently unavailable for patients who cannot undergo contrast-enhanced CT scans due to patient-related issues such as anaphylaxis to the contrast agent, among others. We present here our experience with atypical segmentectomies guided by 3D images reconstructed from nonenhanced CT data.

The genetic concordance and heterogeneity of the two components of pulmonary carcinosarcoma (PCS), carcinoma, and sarcoma, have not been fully elucidated because of its rare occurrence. We performed targeted sequencing of the carcinoma and sarcoma components of four PCSs to identify genetic similarities and differences. Formalin-fixed paraffin-embedded tissue samples were macroscopically or microscopically dissected. DNA was extracted from each component, and genetic alterations were analyzed separately. Moreover, we performed RNA-seq analysis on both components of one PCS to compare differences in gene expression profiles. The carcinoma part consisted of adenocarcinoma in two cases, squamous cell carcinoma in one, and adenosquamous carcinoma in the last. TP53 mutation was observed in three samples from the trunk, although it was detected only in the sarcoma part in one case. No specific driver gene mutation was observed; however, KRAS mutations were observed in one case in the trunk. RNA-seq analysis revealed that the rhabdomyosarcoma component expressed various genes related to muscle development, whereas the carcinoma component did not; and that gene expression overall was completely different between the two components. Our study revealed that the two different components of PCS shared common gene mutations in most cases. Although gene expression was different among components, if driver genes such as KRAS were detected in PCS, molecular targeted therapy could be beneficial even when the tumor contains a sarcoma component.

The lateral costal artery and vein are under recognized yet potentially important vessels for physicians, especially cardiothoracic surgeons. This study sought to determine the prevalence and clinical, anatomical, and radiological features of lateral costal vessels. We retrospectively analyzed lateral costal vessels based on intraoperative images in patients who underwent thoracic surgery at our institute between January 2016 and March 2020. Clinical data and surgical videos were analyzed for patient characteristics, prevalence, length, laterality, and additional anatomical and radiological features. The overall prevalence of lateral costal vessels was 19% and was significantly higher in males than females (22% vs. 14%, p = 0.003). The lateral costal vessels extended beyond the 2nd intercostal space in 74% of the cases, with differing length between the right and left sides in bilateral cases. Lateral costal vessels could be identified intraoperatively using indocyanine green or preoperatively through three-dimensional computed tomography. The prevalence of lateral costal vessels is relatively high and should be acknowledged by physicians prior to procedures involving the vessels.

RAS/BRAF mutations of colorectal cancer (CRC) play a crucial role in carcinogenesis and cancer progression and need to be considered for the therapeutic strategy choice. We used next-generation-sequencing (NGS) technology to assess RAS/BRAF mutation differences between primary CRC and corresponding pulmonary metastases (PMs). We examined the mutation statuses of the KRAS 12/13/61/146, NRAS 12/13/61/146, and BRAF 600 codons in genomic DNA from fresh-frozen or formalin-fixed paraffin-embedded tissues derived from 34 primary lesions and 52 corresponding PMs from 36 patients with CRC. We found RAS mutations in 76% (26/34) of primary CRC lesions and in 86% (31/36) of PMs. While 27% (7/26) of the primary CRC RAS mutations were heterogeneous, all the RAS mutations in PMs were homogeneous. Of the mutations in PMs, 71% (22/31) were KRAS G>A transitions, of which 82% (18/22) were KRAS G12D or G13D. The RAS mutation discordance between primary tumors and PMs was 12.1% (4/33). RAS mutations with the same genotyping were detected in all synchronous and metachronous PMs from 9 patients. We found no BRAF mutations in either primary or pulmonary tissues. Our NGS analysis suggests that RAS mutations of PM of patients with CRC are more common than initially thought. The presence of KRAS mutations in CRC specimens, especially G12D or G13D mutations, seems to promote PM formation.

Although segmentectomy has become a routine procedure, atypical segmentectomies are less popular than their typical counterparts, probably because anatomic and surgical data are lacking. The left superior lingular S

Carbon ion radiotherapy (CIRT) shows higher local control rates and minimal damage to normal lung parenchyma compared with conventional radiotherapy; however, some patients experience local recurrence. The efficacy and safety of salvage surgery after CIRT for non-small-cell lung cancer are unclear. We reviewed clinical, surgical, pathological and prognostic data of 6 patients who underwent salvage surgery after CIRT between 2010 and 2015. All patients were men with a smoking history, and their median age was 67 years. The time from CIRT to surgery was 18 (range 12-24) months. All patients underwent at least lobectomy with mediastinal node dissection. Viable tumour cells were confirmed pathologically in all cases. Five patients required combined resection or extra procedure because of strong adhesions and the possibility of tumour extension; however, none of the patients had a tumour invasion to the adjacent organ. None of the patients had severe complications, perioperative death and local recurrence, and 3 patients are alive without recurrence (range 28-84 months). Salvage surgery appears to be safe and effective. Even though the tumours did not invade the adjacent organs, combined resection was required because of severe adhesion.

Reports of right middle lobe segmentectomy are rare. We report here that anatomical right middle lobe segmentectomy is a relatively simple surgical procedure and can achieve good expansion of the remnant lung for patients with a relatively large right middle lobe.

We report the technical details of minimally invasive open-window thoracostomy using wound edge protectors for postoperative pyothorax caused by a bronchopleural fistula with acute exacerbation of idiopathic pulmonary fibrosis under epidural and local anesthesia.

Video-assisted thoracoscopic surgery (VATS) has gradually been implemented in thoracic surgery, and the VATS approach has now been extended to technically challenging procedures, such as segmentectomy. The definition of VATS segmentectomy is changing over time, and the repertoire of segmentectomy is getting wider with increasing reports on atypical segmentectomy. VATS segmentectomy bears surgical, oncological, and technical advantages; however, there are still areas of controversy, particularly regarding oncological outcomes. The indication of VATS segmentectomy is diverse and is used for treating lung cancer, metastatic lung tumors, or a variety of nonmalignant diseases. It is particularly valuable for the lung-sparing resection of deeply located small nodules or repeated surgery for multiple lung lesions. VATS segmentectomy requires a thorough analysis of segmental anatomy and a tailored preoperative planning with the assessment of surgical margins. Technical challenges include intraoperative navigation, methods to identify and dissect the intersegmental plane, and the prevention of air leakage. This review will discuss the present state of VATS segmentectomy, with a focus on past studies, current indications and techniques, and future view.

Known as a microtubule-destabilizing protein, STMN1 (gene symbol: STMN1) regulates the dynamics of microtubules, cell cycle progress, and chemo-resistance against taxane agents. It is highly expressed in various human cancers and involved in cancer progression as well as poor prognosis. Expression of STMN1 was examined by immunohistochemistry using FFPE tissue sections from 186 patients with lung squamous cell carcinoma (LSCC). Analysis of STMN1 suppression was performed for STMN1 small interfering RNA (siRNA)-transfected LSCC cell lines to determine the change in proliferation, invasive and apoptosis abilities, and paclitaxel sensitivity. The cytoplasmic STMN1 expression in LSCC was higher than in normal tissues. The high expression was significantly associated with vascular invasion (P = 0.0477) and poor prognosis. In addition, the proliferating and invasive abilities were decreased, and the apoptosis ability and paclitaxel sensitivity were increased in STMN1-suppressed LSCC cells compared with control cells. The results suggest that STMN1 is a prognostic factor that also is associated with caner progression and chemo-resistance. Therefore, STMN1 could be a predictor for poor prognosis and a potential therapeutic target in LSCC.

Objectives General thoracic surgeons must be familiar with anatomical variation in the pulmonary vessels and bronchi. Here, we analyzed the bronchovascular pattern of the right middle lobe (RML) and right lower lobe (RLL) of the lung using three-dimensional CT angiography and bronchography (3DCTAB). Methods We reviewed the anatomical patterns of the pulmonary vessels and bronchi in 270 patients using 3DCTAB images. Results The branching patterns of vessels and bronchi of RML and S6 were classified according to the number of stems. The single-stem type was the most common, except in the artery of the RML, for which the two-stem type was the most common. The artery and bronchus of S*, which is an independent segment between S6 and S10, were observed in 20.4% of cases. The branching pattern of A7 (B7) was classified into four types. The A7a (B7a) type was observed in 74.8% of cases, and was the most common. The branching pattern of the artery and bronchus of S8−10 was classified into five and three types, respectively. The A8 and A9 + A10 type, and the B8 and B9 + B10 type, were observed in 68.1 and 80.4% of cases, respectively, and were the most common types. The branching pattern of V8−10 was more complex than that of A8−10 and B8−10. Conclusion We explored the bronchovascular patterns of RML and RLL and their frequencies using a large number of 3DCTAB images. Our data can be used by thoracic surgeons to perform safe and precise lung resections. Electronic supplementary material The online version of this article (doi:10.1007/s11748-017-0754-4) contains supplementary material, which is available to authorized users.

There are only a few detailed reports concerning the prognosticators following surgical resection of pulmonary metastases (PMs) from renal cell carcinoma (RCC). We investigated the prognosis of patients with RCC PMs undergoing pulmonary metastasectomy and identified prognostic factors in a multi-institutional retrospective study. We retrospectively evaluated 84 patients who underwent resection of PMs from RCC between 1993 and 2014. We assessed the clinicopathological characteristics, focusing on the histological findings of PMs. We classified the histology into three types: pure clear cell carcinoma (N = 68), clear cell carcinoma combined with other histology type (N = 8), and non-clear cell carcinoma (N = 8). We examined the relationship between these histological types and the prognosis of patients with PMs from RCC. Complete resection was achieved in 78 patients (93%). The 5-year overall survival rate after metastasectomy was 59.7%. In multivariate analysis, three factors were found to be independent favorable prognostic factors of overall survival after lung metastasectomy [tumor size

Objective Thoracic surgeons must be erudite pulmonary vein variation when performing anatomical segmentectomy. We used three-dimensional CT (3DCT) to accumulate variations of the pulmonary veins of the right upper lobe (RUL) and created a simplified RUL vein model. Methods We reviewed anatomical variations of the RUL pulmonary veins of 338 patients using 3DCT images, and classified them by position related with bronchus. Results Of the “anterior” and “central” RUL veins, all could be classified into 4 types: 2 Anterior with Central types (Iab and Ib), 1 Anterior type, and 1 Central type. The Anterior with Central type was observed in 273 patients (81 %), and was further classified into two types according to the origin of the anterior vein. In the Iab type, the anterior vein originated from V1a to V1b (54 %) whereas, in the Ib type, the anterior vein originated from only V1b (26 %). The Central type, which had no anterior vein, was evident in 23 cases (7 %). These three types could be further divided into three subcategories by reference to the branching pattern of the central vein. The Anterior type, which had no central vein, was evident in 42 cases (12 %), and this type could be further categorized into two types, depending on the branching pattern of the anterior vein. Conclusion We created a simplified RUL vein model to facilitate anatomical segmentectomy. Our models should find wide application, especially when thoracic surgery requiring anatomical RUL segmentectomy is planned. Electronic supplementary material The online version of this article (doi:10.1007/s11748-016-0686-4) contains supplementary material, which is available to authorized users.

The MDM2 protein plays an important role in the regulation of cell proliferation and apoptosis via ubiquitination and proteasome‐mediated degradation of p53. The genetic polymorphism rs2279744 (c.309T>G) of the MDM2 gene is reportedly associated with susceptibility and/or prognosis in various cancers. In this study, we investigated the risk factors for worse survival in patients with lung adenocarcinoma (AC). We examined the association between c.309T>G and the prognosis of lung cancer by retrospectively reviewing 453 lung cancer patients. We studied both, clinicopathological and genetic characteristics, including the c.309T>G, p53 Arg72Pro, EGFR,KRAS, and p53 mutations. Associations between these factors and survival outcome were analyzed using Cox proportional hazards models. The frequencies of MDM2 polymorphisms were T/T, 20.8%; T/G, 48.6%, and G/G, 30.7%. The overall survival (OS) of AC patients with pathological stage I disease and the MDM2 T/T genotype was significantly shorter than that of those with the T/G or G/G genotypes (P = 0.02). Multivariate analysis revealed that the MDM2 T/T genotype was an independent, significant prognostic factor (hazard ratio [HR] = 2.23; 95% confidence interval [CI]: 1.07–4.65; P = 0.03). The MDM2 T/T genotype was predictive of poorer survival in a Japanese population. Genotyping for this polymorphism might predict the clinical outcomes of stage I AC patients.

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.

The technique of medial-basal segment (S

Lung combined neuroendocrine carcinomas (NECs) comprise NEC and non-NEC components, such as adenocarcinoma and squamous cell carcinoma. Mutation of epidermal growth factor receptor (EGFR) often is observed in non-NEC but is very rare in sporadic NEC, which almost always has p53 mutation. Therefore, we hypothesized the following research concept: mutation analysis of EGFR and p53 in each component of combined NEC tissues can provide important information on whether such components originate from the same tumor cells or incidentally arise as collision cancers. We compared the mutations of EGFR and p53 in laser-microdissected NEC and non-NEC from lungs of eight cases affected by combined NEC. We examined the expression of EGFR and NEC markers in the combined NECs by immunohistochemistry. Five of eight cases of combined NEC had the same mutations of EGFR and/or p53 in both non-NEC and NEC. One case had EGFR mutation in only the non-NEC component, and two cases did not have these mutations. Replacement transformation was observed in borderline areas between non-NEC and NEC. The signal of activated EGFR in non-NEC with the same EGFR mutation was more intense than that in NEC components. Our study suggests the mechanism behind the carcinogenesis of lung combined NEC, which is partially caused by the transformation from epithelial carcinoma of non-NEC to NEC.

Background Stathmin-1 regulates microtubule dynamics and is associated with malignant phenotypes in non-small cell lung cancer (NSCLC). This study evaluated its diagnostic value for differentiating between NSCLC and high-grade lung neuroendocrine tumor (HGNET). Methods Stathmin-1 protein expression was assessed by immunohistochemistry in 414 NSCLC (305 adenocarcinoma [AD], 102 squamous cell carcinoma [SCC], 7 large-cell carcinoma), 5 typical carcinoid (low-grade lung neuroendocrine tumor), and 34 HGNET (17 small-cell carcinoma [SCLC] and 17 large-cell neuroendocrine carcinoma [LCNEC]) surgical specimens and 57 NSCLC (29 AD and 28 SCC) and 42 HGNET (17 LCNEC and 25 SCLC) biopsy specimens. We also analyzed stathmin-1 mRNA levels in 81 NSCLCs and 26 HGNETs with the use of reverse transcription-polymerase chain reaction. Results Among NSCLC samples, we saw high stathmin-1 protein expression in only three ADs, one SCC, and one large-cell carcinoma surgical samples, all five of which showed neuroendocrine characteristics in pathologic re-review; and low or intermediate expression in all five typical carcinoid surgical samples and all 57 NSCLC biopsy samples. In contrast, all HGNET surgical (n = 34) and biopsy (n = 42) samples showed high stathmin-1 expression. In reverse transcription-polymerase chain reaction, stathmin-1 expression was significantly higher in HGNET tissues than in NSCLC tissues (p Conclusions Stathmin-1 expression can help in differentiating NSCLC from HGNET.

The aim of this study was to identify risk factors for recurrence in non-small cell lung cancer (NSCLC) patients with lymph node metastases after surgical resection.We reviewed 66 consecutive patients with surgically resected NSCLC who had pathologically proven positive lymph nodes (pN1 or pN2). All patients underwent a preoperative 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) evaluation. We analyzed the recurrence-free survival (RFS) and recurrence-free proportion (RFP) according to the clinicopathological factors.A total of 27 patients were pathologically N1 and 39 were N2. The 5-year overall survival rate and the RFS rate were 47.2 and 27.7 %, respectively. The cut-off values for the SUVmax of the tumor and the lymph node ratio (LNR) were determined to be 6.5 and 0.12, respectively, using a receiver operating characteristics curve analysis. Both univariate and multivariate analyses revealed three significant independent factors for RFS: namely, the SUVmax of the tumor, the LNR, and the use of adjuvant chemotherapy. Only the SUVmax was an independent significant predictor of the RFP.Both the SUVmax and the LNR can serve as prognostic factors for patients with pN + NSCLC. Our study suggests that the LNR could be a stronger prognostic factor than the N classification of the TNM system and the SUVmax may predict recurrence in node-positive NSCLC patients.

Background Thymomas generally arise from the thymus in the anterior mediastinum. Ectopic thymomas arising in the middle mediastinum are rare. We present a case of a thymoma arising from the ectopic thymic tissue in the right paratracheal region. Case presentation The patient was a 67-year-old male who underwent an enhanced-computed tomography examination as preoperative staging for colon cancer. A 20-mm nodule in the right paratracheal region was found incidentally. Fluorodeoxyglucose (FDG) accumulation was detected in this solitary nodule by FDG-positron emission tomography, mimicking an enlarged, possibly malignant lymph node. The tumor was removed by thoracoscopic surgery, and a postoperative pathological diagnosis of type AB thymoma was made. Foci of ectopic thymic tissues were found adjacent to the thymoma. The patient was disease-free and without recurrence 2 years postoperatively. Conclusions Including the present case, 13 cases of ectopic paratracheal thymoma have been reported in the English literature, all of which were found on the right side of the paratracheal region. Although ectopic thymomas in the paratracheal region are rare, thymomas may be considered as a differential diagnosis for a paratracheal nodule.

The diffusing capacity of the lung for carbon monoxide (DLCO) is an indicator of lung damage. We sought to determine whether DLCO is associated with the aggressiveness of lung adenocarcinoma using histopathological indexes, such as tumour differentiation, scar grade, nuclear atypia and the mitotic index.Fifty-seven patients with low DLCO (≤80% of predicted) and 466 patients with normal DLCO (80% of predicted) who underwent R0 resection of lung adenocarcinoma between 2005 and 2012 were retrospectively reviewed. The relationships between the DLCO status and each histopathological index as well as the overall survival were evaluated.Low DLCO had significant relationships with moderate/poor differentiation (79% vs 57% [low DLCO vs normal DLCO]), scar grade 3/4 (37% vs 18%), nuclear atypia 3 (65% vs 30%) and the mitotic index 3 (26% vs 8%). After adjusting for the age, sex, forced expiratory volume in 1 s, smoking status and tumour size, a low DLCO still showed a significant correlation with the histopathological indexes. These histopathological indexes were all significant factors for the overall survival on log-rank tests. In a multivariable Cox regression analysis with 13 clinicopathological variables, moderate/poor differentiation and nuclear atypia Grade 3 were significant histopathological factors for the overall survival (hazard ratios: 2.16 and 1.84; 95% confidence intervals: 1.10-4.51 and 1.06-3.21; P = 0.024 and 0.029, respectively).Our findings regarding the relationship between DLCO and the histopathological indexes of lung adenocarcinoma suggest that lung damage may be associated with carcinogenesis and progression.

Objectives General thoracic surgeons must be familiar with anatomical variations in the pulmonary bronchi and vessels. We analyzed variations in the bronchovascular pattern of the right upper lung lobe using three-dimensional CT angiography and bronchography and then compared our results with those of previous reports. Methods We reviewed anatomical variations in the right upper pulmonary bronchus and vessels of 263 patients using 3DCT angiography and bronchography images obtained using a 64-channel multidetector CT and workstation running volume-rendering reconstruction software. Results Variations in the pulmonary vein were classified into four types: the “anterior-plus-central vein type” was the most common, noted in 219 cases (83.2 %). The “anterior vein type” was evident in 23 cases (8.8 %), a significantly lower incidence than in previous reports (p

The lung is one of the most common organs of metastasis from colorectal cancer (CRC), and we have encountered lung cancer patients with a history of CRC. There have been few studies regarding methods used to discriminate between primary lung cancer (PLC) and pulmonary metastasis from CRC (PM-CRC) based only on preoperative findings. We retrospectively investigated predictive factors discriminating between these lesions in patients with a history of CRC. Between 2006 and 2015, 117 patients with a history of CRC (44 patients with 47 PLC and 73 patients with 102 PM-CRC) underwent subsequent or concurrent resection of pulmonary lesions. We compared the clinical and radiological characteristics of 100 patients with solitary lesions (43 PLC and 57 PM-CRC). Using univariate and multivariate analyses, we examined predictive factors for discrimination of these two lesions. All tumors with findings of ground-glass opacity (GGO) were PLC (n = 19). In a multivariate analysis of 81 radiologically solid tumors, two factors were found to be significant independent predictors of PLC: a history of stage I CRC and presence of pleural indentation. All tumors in 26 patients with either GGO or both a stage I CRC history and pleural indentation were PLC, while most tumors in patients without all three factors were PM-CRC (43/44; 97.7%). The presence or absence of GGO, pathological CRC stage, and pleural indentation could be useful factors to distinguish between PLC and PM-CRC.

The technical details and anatomic features of medial-basal segment (S7) segmentectomy have not been reported. We report here thoracoscopic S7 segmentectomy and S7a subsegmentectomy and explain the anatomic knowledge necessary to perform S7 segmentectomy, especially the importance of recognizing bronchus (B7) branching patterns before surgery.

INTRODUCTION We adopted the use of Penrose drains and Endo Close to secure a good surgical field during laparoscopic pancreatectomy. METHODS We used a Penrose drain with threads ligated on both ends to suspend the stomach. We then pulled the threads out of the body from the side of the trocar or from besides the xiphisternum by using Endo Close. In most cases, 2 Penrose drains were used to retract the stomach. When the greater omentum on the left side of the cardia still blocks the surgical field, we sewed the posterior wall of the stomach onto the dome of the diaphragm. RESULTS The use of 2 Penrose drains and Endo Close were effective to retract the stomach in most cases. However, in 3 cases, we needed to additionally sew the stomach onto the diaphragm to fully open up the field. CONCLUSION This is a simple and effective method to ensure a good surgical field.

The mesenteric vessels have many branching patterns. This study clarified the anatomic relationship between the superior mesenteric vein (SMV), the right colic artery (RCA), and the ileocolic artery (ICA) using 3-dimensional computed tomography (3D-CT). The relationship between the RCA and the right colic vein (RCV) was also examined.Between April 2006 and July 2011, all patients with colorectal cancer underwent multidetector computed tomography (MDCT) before laparoscopic surgery. The 100 most recent consecutive cases were analyzed. 3D-CT images were made by combining arterial angiography, venous angiography, colonography, tumor, lymph node, and duodenal images.The RCA branched from the SMA in 37 cases (37%); of these, 21 had an ICA that crossed anterior to the SMV and 16 had an ICA that crossed posterior. When the ICA crossed anterior to the SMV, all had an RCA that crossed anterior to the SMV, and no posterior RCA was seen. Furthermore, the RCV joined the SMV in 10 cases (27%) and the gastrocolic trunk in 27 cases (73%).Our study clarified the anatomic variety of the vessels in right-sided colon cancer. Preoperative 3D-CT is useful for understanding the anatomy to ensure a safe, precise operation.

Optineurin (OPTN) mutations cause neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and glaucoma. Although the ALS-associated E478G mutation in the UBAN domain of OPTN reportedly abolishes its NF-κB suppressive activity, the precise molecular basis in ALS pathogenesis still remains unclear. Here we report that the OPTN-UBAN domain is crucial for NF-κB suppression. Our crystal structure analysis reveals that OPTN-UBAN binds linear ubiquitin with homology to NEMO. TNF-α-mediated NF-κB activation is enhanced in OPTN-knockout cells, through increased ubiquitination and association of TNF receptor (TNFR) complex I components. Furthermore, OPTN binds caspase 8, and OPTN deficiency accelerates TNF-α-induced apoptosis by enhancing complex II formation. Immunohistochemical analyses of motor neurons from OPTN-associated ALS patients reveal that linear ubiquitin and activated NF-κB are partially co-localized with cytoplasmic inclusions, and that activation of caspases is elevated. Taken together, OPTN regulates both NF-κB activation and apoptosis via linear ubiquitin binding, and the loss of this ability may lead to ALS., Mutations in optineurin are associated with neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, the authors report the structure of the ubiquitin binding domain of optineurin, which binds linear ubiquitin with homology to NEMO, and explore the function of this domain.

SIRPbeta (signal-regulatory protein beta) is a transmembrane protein that is expressed in hematopoietic cells but whose functions are unknown. We have now cloned mouse SIRPbeta cDNA and have shown that the gene is expressed in various tissues in addition to cells of the macrophage lineage. Engagement of SIRPbeta by specific monoclonal antibodies promoted Fcgamma receptor-dependent or -independent phagocytosis in mouse peritoneal macrophages. It also induced marked activation of MAPK and the upstream kinase MEK but weak activation of Akt. MEK inhibitors markedly blocked the promotion of phagocytosis by SIRPbeta, whereas an inhibitor of phosphoinositide 3-kinase partly blocked such response. In addition, inhibitors of myosin light chain kinase or of myosin ATPase blocked the promotion of phagocytosis by SIRPbeta. Furthermore, SIRPbeta induced the formation of filopodia and lamellipodia in macrophages as well as the translocation of activated MAPK to these structures. It also elicited tyrosine phosphorylation of DAP12, Syk, and SLP-76, and a Syk inhibitor blocked the promotion of phagocytosis and activation of MAPK by SIRPbeta. Our results suggest that engagement of SIRPbeta promotes phagocytosis in macrophages by inducing the tyrosine phosphorylation of DAP12, Syk, and SLP-76 and the subsequent activation of a MEK-MAPK-myosin light chain kinase cascade.

We treated a 64-year-old woman with high blood pressure. Catecholamine metabolite levels were elevated in the blood and urine. CT revealed a densely stained tumor on the right side of the descending aorta dorsal to the inferior vena cava. PET-CT revealed abnormal accumulation of (18) F-fluorodeoxyglucose, and (123) I-meta-iodo-benzylguanidine uptake was apparent on scintigraphy. The tumor was determined to be a paraganglioma located on the border between the thoracic and abdominal cavities, and laparoscopic tumorectomy was performed. The patient was placed in the left lateral position. The right lobe of the liver was turned over, and we cut the diaphragm to expose the front of the tumor. We resected the straight artery flowing in from the aorta and removed the tumor safely. Herein, we describe the removal of a paravertebral paraganglioma located in the border of the thoracic and abdominal cavities with a laparoscopic transabdominal-transdiaphragmatic approach.

Our objective was to evaluate the validity of pulmonary metastasectomy for postoperative colorectal cancer with hepatic metastasis and to investigate the role of clinicopathological factors as predictors of outcome.Consecutive patients undergoing pulmonary metastasectomy for colorectal cancer with (group PH, n=27) or without (group P, n=46) a history of hepatic metastasis were included in the study. Clinicopathological variables, including sex, age, site, serum carcinoembryonic antigen level of the primary tumor, disease-free interval, prior hepatic resection, timing of pulmonary metastases, preoperative chemotherapy, type of pulmonary resection, and number, size, and location of pulmonary metastases were retrospectively collected and investigated for prognostic significance.The 5-year survivals were 59.5% (PH) and 70.0% (P) with no significant difference. Among all investigated prognostic variables, sex (female vs male) and the number of pulmonary metastases( 1 vs1) were the most important factors affecting outcome after colorectal resection and pulmonary resection.Pulmonary resection is not contraindicated in clinical practice. The presence of female gender and a single pulmonary metastasis were favorable predictors of survival after complete pulmonary resection for metastatic colorectal cancer.

Somatic mutation in human epidermal growth factor receptor-related 2 gene (HER2) is one of the driver mutations in lung cancer. HER2 mutations are found in about 2% of lung adenocarcinomas (ADCs). Previous reports have been based mainly on diagnostic screening by Sanger sequencing or next-generation sequencing (NGS); however, these methods are time-consuming and complicated. We developed a rapid, simple, sensitive mutation detection assay for detecting HER2 12 base pair-duplicated insertion mutation based on the Eprobe-mediated PCR method (Eprobe-PCR) and validated the sensitivity of this assay system for clinical diagnostics. We examined 635 tumor samples and analyzed HER2 mutations using the Eprobe-PCR method, NGS, and Sanger sequencing. In a serial dilution study, the Eprobe-PCR was able to detect mutant plasmid DNA when its concentration was reduced to 0.1% by mixing with wild-type DNA. We also confirmed amplification of the mutated plasmid DNA with only 10 copies per reaction. In ADCs, Eprobe-PCR detected the HER2 mutation in 2.02% (9/446), while Sanger sequencing detected it in 1.57% (7/446). Eprobe-PCR was able to detect the mutation in two samples that were undetectable by Sanger sequencing. All non-ADC samples were wild-type. There were no discrepancies between frozen and formalin-fixed paraffin-embedded tissues in the nine samples. HER2 mutations detected by NGS data validated the high sensitivity of the method. Therefore, this new technique can lead to precise molecular-targeted therapies.

Most thoracic surgeons have experienced difficulty dissecting the pulmonary hilus because of scarring. In such potentially dangerous situations, we advocate a method of clamping and severing the pulmonary lobar root structure en masse. The aim of this study was to evaluate en masse lobectomy, particularly considering the constellation of pulmonary vessels and the bronchus. Twelve patients (median age 70 years) underwent en masse lobectomy. We retrospectively evaluated the surgical procedures and clinical outcomes. Care was taken to consider the remaining vessels and bronchus, which regulate the direction of device placement. Seven patients had inflammatory lung disease, four had primary pulmonary carcinoma, and one had suffered blunt chest trauma. Ten operations were elective and two were emergent. Lobectomy included the right upper lobe in two cases, the right middle lobe in three, the right lower lobe in two, the right middle-lower lobe in two, and the left lower lobe in three. A stapler was used in ten patients, and sutures were applied in three (both were used in one case). Morbidities included a pyothorax and a persistent air leak; both made a recovery. Mortality included one emergency case of acute respiratory distress syndrome. No bronchopleural or bronchovascular fistulas occurred. We believe that the en masse lobectomy is an alternative and necessary technique in critical or unexpected situations, possibly as a last resort. Trauma and severe inflammation may be good indications for en masse lobectomy.

A postoperative lung cancer patient presented with lymphadenopathy, pleural thickening, and 18F-fluorodeoxyglucose (FDG) uptake on a positron emission tomography–computed tomography (PET–CT) scan. Lung cancer recurrence was initially suspected, but bilateral submandibular masses with 18F-FDG uptake indicated the possibility of a systemic disease, such as Mikulicz’s disease. High serum immunoglobulin G4 (IgG4) and IgG4-positive plasma cell infiltration in the submandibular glands led to the diagnosis of IgG4-related disease. After systemic steroid therapy, 18F-FDG uptake decreased in both the submandibular glands and the suspected recurrent lesions.

Aortocaval fistula (ACF) is a well-known but uncommon complication of ruptured abdominal aortic aneurysm (AAA). Even with attentive care, oversight of ACFs may occur in emergency cases. Because mortality due to ACF is high, a rapid multidirectional analysis of the preoperative state leading to a correct diagnosis is essential. Here, we report the case of an 82-year-old man with a ruptured AAA and ACF. He presented with multiple organ failure that was initially attributed to congestive heart failure. He underwent emergent surgery and was diagnosed intraoperatively as having an AAA with ACF. He left the hospital 1 month after the operation without complications.