Molecular and expressional characterization of tumor heterogeneity in pulmonary carcinosarcoma.

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.

A minimally invasive technique for stabilizing the diaphragm on the thoracic wall after blunt chest trauma: the "lifting-up method".

Most traumatic diaphragmatic tears are located centrally or radially and may be amenable to repair by direct suturing or suturing with a surgical patch. However, diaphragmatic tears, such as those immediately adjacent to the costal margin, are uncommon. We describe how we repaired this type of tear using a needle loop retractor to pass a 2-0 braided suture through the chest wall on both sides of the rib to suture the torn diaphragm to the chest wall. Our technique is more physiologically and anatomically consistent than previously reported techniques. We have termed this technique the "lifting-up method", which we believe to be an easy and useful technique for repairing traumatic diaphragmatic injuries with no seam allowance.

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

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

[Initial report of uniportal video-assisted thoracoscopic lobectomy in Japan].

To date, more than 100 reports of several major pulmonary resections through a uniportal approach have been published. However, there have been no reports of uniportal thoracoscopic lobectomy in Japan. We present herein a successful case of uniportal thoracoscopic right lower lobectomy through a 3.5-cm incision for 84- year-old female patient with primary lung cancer (clinical stage I A). Postoperative course was uneventful and she discharged from the hospital on day 5 postoperatively. Pathological diagnosis was primary adenocarcinoma of T1aN0M0, stage I A.

Prognosis of non-small cell lung cancer with postoperative regional lymph node recurrence.

BACKGROUND: Regional lymph node recurrence after radical surgery for non-small cell lung cancer (NSCLC) is an oligo-recurrent disease; however, no treatment strategy has been established. In the present study we aimed to determine the clinical outcomes of postoperative regional lymph node recurrence and identify prognostic predictors in the era of molecular-targeted therapy. METHODS: We retrospectively analyzed data on clinical characteristics and outcomes of patients with regional lymph node recurrence after surgery who underwent treatment for NSCLC between 2002 and 2022. RESULTS: A total of 53 patients were included in this study. The median time between surgery and detection of recurrence was 1.21 years. Radiotherapy (RT) alone and chemoradiotherapy (CRT) were performed in 38 and six patients, respectively. Driver gene alterations were detected in eight patients (EGFR: 6, ROS1:1, and BRAF: 1) and programmed death-ligand 1 (PD-L1) expression was examined in 22 patients after 2016. Median progression-free survival (PFS) and overall survival (OS) after lymph node recurrences were 1.32 and 4.34 years, respectively. Multiple lymph node recurrence was an independent prognostic factor for PFS, whereas driver gene alteration was the only prognostic factor for OS. There was no significant difference in the OS between patients stratified according to the initial treatment modality for lymph node recurrence. CONCLUSION: Our results suggest that the number of tumor recurrences may correlate with PFS, while detection of driver gene alterations could guide decision-making for the appropriate molecular-targeted therapy to achieve longer OS.

[Lung metastasectomy for postoperative colorectal cancer in patients with a history of hepatic metastasis].

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 vs >1) were the most important factors affecting outcome after colorectal resection and pulmonary resection. CONCLUSIONS: 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.

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.

Autoimmune alopecia areata due to thymoma without myasthenia gravis: a case report.

BACKGROUND: Thymoma is associated with autoimmune diseases. Myasthenia gravis is frequently associated with thymoma, but cases of thymoma complicated by alopecia areata are very rare. In this report, we present a case of thymoma associated with alopecia areata, but without Myasthenia gravis. CASE PRESENTATION: A 60-year-old woman had a complaint of rapid progression of alopecia areata. A hair follicular biopsy was performed, which showed the infiltration of CD8-positive lymphocytes. She was prescribed topical steroids for 2 months prior to surgery, but her hair loss was not improved. Screening computed tomography showed a mass in the anterior mediastinum, which was suspected to be a thymoma. Myasthenia gravis was ruled out because she had no relevant symptoms or physical findings, and no anti-acetylcholine receptor antibodies were detected in serum. We performed a transsternal extended thymectomy based on a diagnosis of thymoma Masaoka stage I, without myasthenia gravis. Pathological examination showed Type AB thymoma, Masaoka stage II. The chest drainage tube was removed on postoperative day 1, and the patient was discharged on postoperative day 6. The patient has continued topical steroids and showed improvement 2 months postoperatively. CONCLUSIONS: Although alopecia areata is a rare complication in thymoma cases without myasthenia gravis, thoracic surgeons need to keep this condition in mind because alopecia reduces the patient's quality of life.

Anatomy of the lung revisited by 3D-CT imaging.

The anatomy of the lung was originally described based on data acquired from cadaveric studies and surgical findings. Over time, computed tomography (CT) and three-dimensional (3D) imaging techniques have been developed, allowing for reconstruction and understanding of lung anatomy in a more intuitive way. The wide adoption of 3D-CT imaging technology has led to a variety of anatomical studies performed not only by anatomists but also by surgeons and radiologists. Such studies have led to new or modified classification systems, shed light on lung anatomy from a useful surgical viewpoint, and enabled us to analyze lung anatomy with a focus on particular anatomical features. 3D images also allow for enhanced pre- and intra-operative simulation, improved surgical safety, enhanced educational utility, and the capacity to perform large-scale anatomical studies in shorter time frames. We will review here the key features of 3D-CT imaging of the lung, along with representative anatomical studies regarding (I) general lung anatomy, (II) anatomy of the right and left lobes, and (III) features of interlobar vessels. The current surge of 3D imaging analysis shows that the field is growing, with the technology continuing to improve. Future studies using these new and innovative methodologies will continue to refine our understanding of lung anatomy while enhancing our ability to perform safe and effective surgical resections.

A "Catlike Cry" as a Symptom of Congenital Tracheoesophageal Fistula.

Congenital tracheoesophageal fistula is usually diagnosed at an early age, but may remain undetected into adulthood if atresia is absent and if the fistula is small. A tracheoesophageal fistula should be suspected in patients with unexplained episodes of respiratory distress or pneumonia; however, more subtle signs can be an important symptom for early recognition of the disease. Ono's sign is a well-known symptom of tracheoesophageal fistula, characterized by paroxysmal coughing triggered by swallowing of fluids. In the present case, air movement between the esophagus and the trachea through the fistula caused a high-pitched sound, which the patient described as a "catlike cry." The high-pitched sound ceased after surgical closure of the fistula. We report here the symptom of "catlike cry" as one manifestation of tracheoesophageal fistula.

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.

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.

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.

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.

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.

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.

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.

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.

Thoracoscopic right upper lobectomy after an initial anatomic pulmonary resection of the lower lobe.

It is challenging to redo an anatomical pulmonary resection on the ipsilateral side because of the adhesions or dense fissures caused by the initial anatomic pulmonary resection. Few reports describe surgical techniques for addressing these challenges, especially using a minimally invasive thoracoscopic approach instead of standard thoracotomy. Here, we demonstrate a thoracoscopic right upper lobectomy after an initial anatomic pulmonary resection of the right lower lobe and explain the nuances of performing it.