Risk factors for late-onset pulmonary fistula after pulmonary segmentectomy.

Background: Late-onset pulmonary fistula (LOPF) is a well-described complication after segmentectomy, but the precise incidence and risk factors are still unclear. We aimed to determine the incidence of, and risk factors for, LOPF development after segmentectomy. Methods: A single-institution retrospective study was performed. A total of 396 patients who underwent segmentectomy were enrolled. Perioperative data were analyzed to identify the risk factors for LOPF requiring readmission according to univariate and multivariate analyses. Results: The overall morbidity rate was 19.4%. The incidence rates of prolonged air leak (PAL) in the early phase and LOPF in the late phase were 6.3% (25/396) and 4.5% (18/396), respectively. The most common surgical procedures with LOPF development were segmentectomy of the upper-division (n=6) and S6 (n=5). With a univariate analysis, presence of smoking-related diseases did not affect LOPF development (P=0.139). Conversely, segmentectomy with cranial side free space (CSFS) in the intersegmental plane and use of electrocautery to divide the intersegmental plane were associated with a high risk of LOPF development (P=0.006 and 0.009, respectively). A multivariate logistic regression analysis showed that segmentectomy with CSFS in the intersegmental plane and use of electrocautery were independent risk factors for LOPF development. Approximately 80% of patients who developed LOPF recovered by prompt drainage and pleurodesis without reoperation, whereas the remaining patients developed empyema due to delayed drainage. Conclusions: Segmentectomy with CSFS is an independent risk factor for LOPF development. Careful postoperative follow up and rapid treatment are necessary to avoid empyema.

Clinicopathological features and surgical outcomes of lobectomy combined with segmentectomy: a cohort study.

Background: Segmentectomy is a standard procedure, and there is considerable data on routine segmentectomies. However, there are only few reports on lobectomy performed in combination with segmentectomy (lobectomy + segmentectomy). Thus, we aimed to clarify the clinicopathological features and surgical outcomes of lobectomy + segmentectomy. Methods: We reviewed patients who underwent lobectomy + segmentectomy between January 2010 and July 2021 at Gunma University Hospital, Japan. We comparatively analyzed clinicopathological data of patients who underwent lobectomy + segmentectomy and those who underwent lobectomy in combination with wedge resection (lobectomy + wedge resection). Results: We collected data from 22 patients who underwent lobectomy + segmentectomy and 72 who underwent lobectomy + wedge resection. Lobectomy + segmentectomy was mainly performed to treat lung cancer, and the median number of resected segments was 4.5 and the median number of lesions was 2. Lobectomy + segmentectomy was associated with a higher rate of thoracotomy and a longer operation time. Incidence of overall complications, including pulmonary fistula and pneumonia was higher in the lobectomy + segmentectomy group. However, there were no significant differences in the length of drainage, major complications, and mortality. For lobectomy + segmentectomy, the only left-sided procedure was a left lower lobectomy + lingulectomy, whereas procedures were diverse on the right side, mostly combining a right upper or middle lobectomy with atypical segmentectomies. Conclusions: Lobectomy + segmentectomy was performed for (I) multiple lung lesions, (II) lesions invading an adjacent lobe, or (III) lesions with a metastatic lymph node invading the bronchial bifurcation. Although lobectomy + segmentectomy is a lung-preserving procedure that can benefit patients with multiple or advanced diseases involving two lobes, this procedure should still be performed following a careful patient selection process.

Video-assisted thoracoscopic segmentectomy with combined chest wall resection: A case report.

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.

Clinical and anatomical features of the lateral costal artery and vein.

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.

Complex vs. simple segmentectomy: comparing surgical outcomes in the left upper division.

BACKGROUND: 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 (S1+2 + S3) is frequently performed as a sublobar resection because of its technical simplicity. However, the differences in surgical outcomes between simple and complex segmentectomies remain unclear. METHODS: We 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. RESULTS: In total, 118 patients were included: 65 in the simple group and 53 in the complex group (S1+2: 25, S3: 15, others: 13). There were no significant differences in surgical time or duration of postoperative chest drainage. However, the blood loss volume was significantly smaller in the complex group than in the simple group (12 vs. 36 mL, p = 0.023), and major complications tended to occur less frequently in the complex group than in the simple group (3.8 vs. 13.8%, p = 0.061). Among patients who underwent intentional segmentectomy for primary lung cancer (n = 61), major complications were significantly less common in the complex group (p = 0.006). CONCLUSIONS: Complex 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.

Surgical outcomes after multiple segmentectomy: a cohort study.

BACKGROUND: Segmentectomy is now a common treatment option for both lung cancer and metastatic lung tumors with increasing data and evidence. However, data on multiple segmentectomy of different lobes are scarce. Our objective was to clarify the clinicopathological features of multiple segmentectomy. METHODS: We reviewed patients who underwent segmentectomy between January 2010 and December 2019 at Gunma University Hospital. Multiple segmentectomy was defined as segmentectomy of different lobes during the same operation, in contrast to single segmentectomy, which was defined as segmentectomy of a single lobe. Clinicopathologic, operative, and postoperative results were compared between multiple segmentectomy and single segmentectomy. RESULTS: There were 324 patients who underwent single segmentectomy and 11 patients (12 cases) who underwent multiple segmentectomy. Multiple segmentectomy was mostly performed for treatment of metastatic lesions rather than lung cancer. The median number of resected segments was 1 (range, 1-5) in the single segmentectomy group and 3 (range, 2-4) in the multiple segmentectomy group. The median number of resected lung lesions was 3.5 in the multiple segmentectomy group. Multiple segmentectomy was associated with longer operative time, more bleeding, and longer drainage period and postoperative stay than the single segmentectomy group. There were no significant differences in severe complications as well as 30- and 90-day mortality. CONCLUSIONS: Multiple segmentectomy is a lung-preserving procedure that can be considered for patients with multiple lung lesions and has feasible postoperative outcomes.

Superior Lingular S4 Segmentectomy.

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 S4 segment is considered relatively small, usually resected along with other segments. However S4 segment size varies among patients, and resection of this single segment can be a valuable lung-preserving procedure in carefully selected patients with tumors located at the border of the upper division and lingular segments. We present here the anatomic and surgical features required for a methodologic left S4 segmentectomy based on our experience and the literature.

Quantitative analysis of metabolic parameters at 18F-fluorodeoxyglucose positron emission tomography in predicting malignant potential of anterior mediastinal tumors.

To evaluate the utility of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for predicting the malignancy of anterior mediastinal tumors, the present study retrospectively examined a total of 105 consecutive patients who underwent surgical resection of anterior mediastinal tumors at Gunma University Hospital after undergoing a preoperative FDG-PET scan. Patients were divided into benign and malignant groups in accordance with the following three classification systems: i) Clinical classification, benign or malignant (thymoma and carcinoma); ii) recurrence-based classification, low-risk recurrence (benign and low-risk thymoma) or high-risk recurrence (high-risk thymoma and carcinoma); and iii) pathological classification, benign (benign and thymoma) or malignant (carcinoma). The present study analyzed the differences between the benign and malignant groups in terms of FDG-PET parameters, including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The malignant group exhibited a significantly greater SUVmax than the benign group according to all classification systems. By contrast, there was only a slight difference between groups in volume-based metabolic parameters (MTV and TLG) using the clinical classification, and no intergroup differences using the recurrence-based and pathological classifications. The area under the curve in receiver-operating characteristic curve analysis for predicting malignancy was significantly greater for SUVmax than for volume-based metabolic parameters using all classification methods. The respective optimal cut-off value, sensitivity and specificity of SUVmax to predict malignancy were 1.77, 92.0 and 87.0% for the clinical classification, 2.54, 93.6 and 60.3% for the recurrence-based classification, and 5.15, 78.9 and 90.7% for the pathological classification. SUVmax was the most useful parameter for predicting the malignancy of anterior mediastinal tumors.

Right upper lobe segmentectomy guided by simplified anatomic models.

BACKGROUND: To standardize the technical strategy for right upper lobe (RUL) segmentectomy, we previously developed simplified 3-dimensional (3D) anatomic models that classify the RUL anatomy into 14 patterns according to the branching pattern of bronchi and veins. We aimed to study the surgical outcome of RUL segmentectomy guided by these simplified anatomic models. METHODS: Patients were classified into the anatomic models, and the approach to the intersegmental veins was selected accordingly. The intersegmental vein and corresponding intersegmental plane were as follows: V1b (the apicoanterior plane), V2a (the apicoposterior plane), and V2c (the posteroanterior plane). Clinicopathologic characteristics and short- and long-term outcomes were analyzed retrospectively. RESULTS: Thirty-four consecutive patients who underwent thoracoscopic RUL segmentectomy guided by simplified anatomic models between January 2016 and December 2019 at Gunma University were analyzed. All the patients were classified into a model: anterior + central Iab type (47%), anterior + central Ib type (41%), anterior II type (12%), or central III type (0%). The standard approaches to intersegmental veins were an anterior approach for V1b, a posterobronchial approach for V2a, and an interlobar approach for V2c. The approach to intersegmental or intrasegmental veins was modified according to the anatomic model in 4 cases (12%). The median operative time, blood loss, and hospital stay were 222 minutes, 19 grams, and 7 days, respectively. Prolonged air leakage was observed in 1 patient. CONCLUSIONS: Segmentectomy guided by simplified anatomic models promotes anatomic classification, development of a standardized approach for segmental vein identification, and acceptable outcomes, which can facilitate the implementation of RUL segmentectomy.

Significance of RAS mutations in pulmonary metastases of patients with colorectal cancer.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinicopathological features of small-sized peripheral squamous cell lung cancer.

Recent advances in imaging technology have enhanced the detection rate of small-sized peripheral lung cancers. The present study aimed to identify the clinicopathological differences between patients with small-sized peripheral squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Patients with lung cancer who underwent radical surgical resection at Gunma University Hospital between July 2007 and October 2012 were retrospectively analyzed. Patients who exhibited small-sized peripheral tumors (pathological size, ≤2 cm) located within the outer-third of the lung field on preoperative computed tomography were enrolled in the present study. A total of 26 patients were diagnosed with SCC and 214 with ADC. The results revealed that patients with SCC exhibited higher rates of pleural invasion, vascular invasion and lymphatic invasion compared with ADC patients. Additionally, the rate of postoperative recurrence was higher in patients with SCC compared with ADC patients. Patients with ADC were subsequently into two groups: Solid ADCs (sADC) and non-solid ADCs (nsADC), which included pure ground glass nodules and part-solid ADCs. The results revealed that the incidence of pleural invasion, vascular invasion and lymphatic invasion, and the rate of postoperative recurrence in patients with sADCs were similar to those with SCC, but were also significantly higher when compared with nsADC patients. The present study concluded that patients with SCC and sADC may not be suitable candidates for sublobar resection, despite exhibiting small tumors that are located in the peripheral lung.

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.

Carbonic anhydrase 9 expression is associated with poor prognosis, tumor proliferation, and radiosensitivity of thymic carcinomas.

INTRODUCTION: Thymic epithelial tumors (TETs) comprise several histologies of thymoma and thymic carcinomas (TCs), and TC frequently metastasizes and causes death. We therefore aimed here to identify key molecules closely related to prognosis and their biological roles in high-risk TETs, particularly TCs. RESULTS: RNA sequence analysis demonstrated that hypoxia-related genes were highly expressed in TETs. The expression of the hypoxia-related gene CA9 was noteworthy, particularly in TCs. Immunohistochemical analysis revealed that CA9 was expressed in 81.0% of TCs and 20.7% of all TET samples. CA9 expression was significantly associated with Masaoka stage, WHO classification, and recurrence-free survival after tumor resection (P = 0.005). The down-regulation of CA9 transcription in TC cell lines by small interfering RNAs significantly inhibited CA9 expression, which inhibited proliferation and increased sensitivity to irradiation. CONCLUSIONS: CA9 expression may serve as a significant prognostic marker of TETs and therefore represents a potential target for the development of novel drugs and radiation-sensitizing therapy designed to improve the outcomes of patients with TCs. MATERIALS AND METHODS: We performed comprehensive transcriptome sequencing of 23 TETs and physiologic thymic specimens to identify genes highly and specifically expressed in high-risk TETs, particulary TCs. We performed immunohistochemical analysis of 179 consecutive surgically resected TETs to evaluate the significance of the association of protein expression with clinicopathological features and prognosis. The biological significance of the most promising prognostic marker was further studied using the TC cell lines, Ty-82 and MP57.

Genetic and Immunohistochemical Studies Investigating the Histogenesis of Neuroendocrine and Carcinomatous Components of Combined Neuroendocrine Carcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Stathmin-1 Is a Useful Diagnostic Marker for High-Grade Lung Neuroendocrine Tumors.

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 < 0.001). CONCLUSIONS: Stathmin-1 expression can help in differentiating NSCLC from HGNET.

Minimally Invasive Open-Window Thoracostomy Using Wound Edge Protectors.

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.

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.

The impact of histology and ground-glass opacity component on volume doubling time in primary lung cancer.

BACKGROUND: Correlations between volume doubling time (VDT) of primary lung cancer (PLC), histology, and ground glass opacity (GGO) components remain unclear. The purpose of this study was to evaluate and compare VDT of PLC in terms of histology and presence or absence of GGO components. METHODS: A total of 371 surgically resected PLCs from 2003 to 2015 in our institute were retrospectively reviewed. The VDT was calculated both from the diameters of the entire tumor and of consolidation by using the approximation formula of Schwartz. RESULTS: The median VDTs of adenocarcinoma, squamous cell carcinoma, and others (large cell neuroendocrine carcinomas, small cell lung carcinomas, pulmonary pleomorphic carcinomas, and large cell carcinomas combined) were 261, 70, and 70 days, respectively; these differ significantly (P<0.001). All PLCs with GGO were adenocarcinomas. The VDT of adenocarcinomas with GGO was significantly longer than that of those without GGO (median VDT: 725 and 177 days, respectively), squamous cell carcinomas, and others. When the VDT calculated from the maximum diameter of consolidation component was compared, adenocarcinomas with GGO also showed significantly slower growth than those without GGO (median VDT: 248 versus 177 days, respectively, P=0.040). CONCLUSIONS: The VDT of PLCs is longest for adenocarcinomas. VDT was significantly longer in adenocarcinomas with GGO components than in those without such components, irrespective of VDT calculated on the basis of either the entire tumor diameter or consolidation diameter.