Relevance of robotic surgery for thymoma: a narrative review.

Background and Objective: Thymectomy with median sternotomy is the gold standard for thymoma and myasthenia gravis, although minimally invasive procedures such as robot-assisted surgery have recently become more common. However, the superiority of these approaches has not been established, and they are infrequently recommended for localized lesions. The International Thymic Malignancies Interest Group warned that despite the perceived reduction in length of hospital stay and pain, the benefits of these approaches compared to the open approach have not been fully substantiated and that prospective collaborative data collection is critical in defining the value of these techniques. Whether thymectomy is necessary for stage I thymomas in the absence of myasthenia gravis or anti-acetylcholine receptor antibodies is also unclear. This study reviews and discusses the literature on this subject. Methods: A narrative review was conducted using PubMed and Scopus databases. Original research articles comparing robotic to video-assisted thoracic surgery or to open thymectomy for thymomas were included. A comparison of partial resection and total thymectomy (thymothymectomy) for thymomas was also conducted. Key Content and Findings: Perioperative outcomes such as blood loss, operative duration, complications, and length of hospital stay were better for robot-assisted resection of early-stage thymomas than for open thymoma surgery. It would be premature to consider partial resection as an appropriate treatment option for thymomas. Conclusions: Robotic thymothymectomy is safe with effective and promising long-term results and oncological and surgical outcomes in patients with thymoma. Robotic thymectomy can become the standard procedure in patients with early-stage thymomas.

Comparison of imaging changes in pulmonary artery diameter at the occlusion site using silk or metal clamps for pulmonary artery troubles.

OBJECTIVES: We analysed our clinical experience using silk sutures [the double-loop technique (DLT)] or DeBakey type vascular clamp (DeBakey clamp) for pulmonary artery (PA) troubles during anatomical lung resection to validate its practicality and safety. METHODS: We retrospectively reviewed the records of patients who underwent either of the above clamping techniques during anatomical lung resection at our hospital between April 2007 and August 2022. We measured the PA diameter at the occlusion site on computed tomography images acquired within 1 year pre- and postoperatively. The difference between pre- and postoperative diameters of the occlusion sites was calculated as the change in the PA diameter. We zoned the occlusion site of the PA to adjust for variation. PA deformation was evaluated as an adverse event caused by clamping. RESULTS: Ultimately, 27 and 26 patients who underwent the DLT and DeBakey clamp, respectively, were included. No additional injury due to the clamp procedure was found in either group. For zone R1/L1, defined as the main PA, the median changes in the PA diameter were 0.02 (-0.7 to 0.27) mm for the DLT and 0.36 (-0.28 to 0.89) mm for the DeBakey clamp. No significant differences were observed between the 2 groups (P = 0.106). Furthermore, no aneurysms, dissections, or stenoses were found in either group. CONCLUSIONS: The DLT and DeBakey clamp had only minimal effects on the occlusion site of the PA. The DLT is a practical thoracoscopic technique for PA bleeding when primary haemostasis has been achieved.

The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells.

Tight junction (TJ) protein cingulin (CGN) and transcription factor forkhead box protein O1 (FOXO1) contribute to the development of various cancers. Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for some cancers. HDAC inhibitors affect the expression of both CGN and FOXO1. However, the roles and regulatory mechanisms of CGN and FOXO1 are unknown in non-small cell lung cancer (NSCLC) and normal human lung epithelial (HLE) cells. In the present study, to investigate the effects of CGN and FOXO1 on the malignancy of NSCLC, we used A549 cells as human lung adenocarcinoma and primary human lung epithelial (HLE) cells as normal lung tissues and performed the knockdown of CGN and FOXO1 by siRNAs. Furthermore, to investigate the detailed mechanisms in the antitumor effects of HDAC inhibitors for NSCLC via CGN and FOXO1, A549 cells and HLE cells were treated with the HDAC inhibitors trichostatin A (TSA) and Quisinostat (JNJ-2648158). In A549 cells, the knockdown of CGN increased bicellular TJ protein claudin-2 (CLDN-2) via mitogen-activated protein kinase/adenosine monophosphate-activated protein kinase (MAPK/AMPK) pathways and induced cell migration, while the knockdown of FOXO1 increased claudin-4 (CLDN-4), decreased CGN, and induced cell proliferation. The knockdown of CGN and FOXO1 induced cell metabolism in A549 cells. TSA and Quisinostat increased CGN and tricellular TJ protein angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) in A549. In normal HLE cells, the knockdown of CGN and FOXO1 increased CLDN-4, while HDAC inhibitors increased CGN and CLDN-4. In conclusion, the knockdown of CGN via FOXO1 contributes to the malignancy of NSCLC. Both HDAC inhibitors, TSA and Quisinostat, may have potential for use in therapy for lung adenocarcinoma via changes in the expression of CGN and FOXO1.

[Crucial Techniques for Chest Tube Placement and Postoperative Management].

Postoperative management of thoracic surgery with an indwelling chest tube is common, and knowledge about it is essential. A postoperative chest tube has four roles:1) to reinflate the lung, 2) to observe the condition of the thoracic cavity and acquire information regarding the outcomes, 3) to prevent complications, and 4) to treat pulmonary air leaks and empyema (chemical pleurodesis et ct). Although postoperative complications have decreased in recent years following advances in video-assisted thoracoscopic surgery( VATS) and devices such as stapling devices and vascular sealing systems (VSS), postoperative chest tube placement is still common. Therefore, a thorough knowledge of chest tube management is extremely important in thoracic surgery. Here, we have described, in detail, the management of a postoperative chest tube at our hospital.

Experimental and histological evaluation of different clamp technique for pulmonary artery.

OBJECTIVES: The double-loop technique has been used in our clinical settings for pulmonary arterioplasty and/or injured artery repair during thoracoscopic anatomical lung resection. We evaluated the pressure resistance capacity and intimal load to determine the effectiveness and safety of the double-loop technique. METHODS: The double-loop technique, DeBakey clamp, Fogarty clamp, endovascular clips and vessel loop technique were evaluated. During an experimental study, a polyvinyl alcohol main pulmonary artery model, manometer and in-deflation device were used to measure the burst pressure. The maximum clamp pressure was measured using a pressure-measuring film. Each measurement was performed 10 times. During the histological study, we measured the burst pressure and evaluated the intimal damage of the human pulmonary artery associated with the double-loop technique and DeBakey clamp. RESULTS: The experimental burst pressure (mmHg) and maximum clamp pressure (MPa) between the double-loop technique and DeBakey at the third notch were not significantly different (24.6 ± 2.8 and 21.8 ± 2.8, P = 0.094; 1.54 ± 0.12 and 1.49 ± 0.12, P = 0.954). During the histological study, the burst pressures of the double-loop technique and DeBakey at the third notch were also not significantly different (P = 0.754). Furthermore, the double-loop technique resulted in only intimal deformation in each five samples. CONCLUSIONS: The double-loop technique is feasible for thoracoscopic anatomical lung resection because it has similar pressure resistance capacity and intimal load as DeBakey at the 3rd notch.

Metastatic pulmonary pleomorphic carcinoma replaced by a granulomatous lesion after spontaneous regression and PD-1 blockade-induced regression: can epithelioid granuloma be a histological hallmark of cancer immunity?

Immune checkpoint inhibitors (ICIs) for various types of malignancy, including non-small-cell lung cancer, have improved prognosis in some cases. Granuloma formation after ICI administration suggests a tumor antigen-specific cytotoxic T cell response with abundant interferon-gamma production, which can be used to estimate the curative effect of ICIs. In this report, we present a case with a resected lung lesion, clinically suspected to be lung cancer, that consisted of a granulomatous lesion. A tumor was also found in the duodenum that was presumed to be derived from the pulmonary pleomorphic carcinoma. Duodenal tumor cells highly expressed PD-L1, suggesting PD-1/PD-L1 axis-mediated immune escape. As expected, pembrolizumab induced a complete response for the duodenal lesion. Interestingly, in histopathological analysis, the duodenal lesion was also replaced by an epithelial granuloma and multinucleated giant cells. We conclude that autoimmunity regressed the untreated primary lung lesion spontaneously, while the metastatic duodenal lesion responded to PD-1 blockade. Tumor-associated epithelioid granulomas, even before ICI administration, may be an important pathological finding indicating an immune response with interferon-gamma production by cytotoxic T cells to the tumor.

Downregulation of angulin-1/LSR induces malignancy via upregulation of EGF-dependent claudin-2 and TGF-ß-dependent cell metabolism in human lung adenocarcinoma A549 cells.

Abnormal expression of bicellular tight junction claudins, including claudin-2 are observed during carcinogenesis in human lung adenocarcinoma. However, little is known about the role of tricellular tight junction molecule angulin-1/lipolysis-stimulated lipoprotein receptor (LSR). In the lung adenocarcinoma tissues examined in the present study, expression of claudin-2 was higher than in normal lung tissues, while angulin-1/LSR was poorly or faintly expressed. We investigated how loss of angulin-1/LSR affects the malignancy of lung adenocarcinoma cell line A549 and normal human lung epithelial (HLE) cells. The EGF receptor tyrosine kinase inhibitor AG1478 prevented the increase of claudin-2 expression induced by EGF in A549 cells. Knockdown of LSR induced expression of claudin-2 at the protein and mRNA levels and AG1478 prevented the upregulation of claudin-2 in A549 cells. Knockdown of LSR induced cell proliferation, cell migration and cell metabolism in A549 cells. Knockdown of claudin-2 inhibited the cell proliferation but did not affect the cell migration or cell metabolism of A549 cells. The TGF-ß type I receptor inhibitor EW-7197 prevented the decrease of LSR and claudin-2 induced by TGF-ß1 in A549 cells and 2D culture of normal HLE cells. EW-7197 prevented the increase of cell migration and cell metabolism induced by TGF-ß1 in A549 cells. EW-7197 prevented the increase of epithelial permeability of FITC-4kD dextran induced by TGF-ß1 in 2.5D culture of normal HLE cells. In conclusion, downregulation of angulin-1/LSR induces malignancy via EGF-dependent claudin-2 and TGF-ß-dependent cell metabolism in human lung adenocarcinoma.

[Mullerian Cyst in the Posterior Mediastinum Resected by Robot-assisted Thoracic Surgery:Report of a Case].

Mullerian cyst in the posterior mediastinum is a rare disorder. We report on the case of a woman in her 40s with a cystic nodule which is located in the right posterior mediastinum next to the vertebra at the level of tracheal bifurcation. The tumor was suggested to be cystic by preoperative magnetic resonance imaging (MRI). The tumor was resected with robot-assisted thoracic surgery. Pathology by hematoxylin-and-eosin (H&E) revealed a thin-walled cyst lined by ciliated epithelium without cellular atypia. The diagnosis of Mullerian cyst was confirmed by immunohistochemical staining which showed the positive findings for estrogen receptor (ER) and progesterone receptor of the lining cells.

[Novel Surgical Techniques for Lung Segmentectomy of Malignant Lung Tumors].

For a long time, lobectomy and lymph node dissection have been the standard surgery for treating non-small cell lung cancer. Recently, segmentectomy has been introduced as an alternative surgical procedure for treating early-stage lung cancer. Moreover, a growing number of segmentectomies are performed due to the increasing number of elderly patients, and the expansion of indications, including early- stage lung cancer with a ground glass nodule or peripheral nodule under 2 cm in diameter. However, the use of segmentectomy remains under debate. We have been performing thoracoscopic lung segmentectomy for malignant lung tumors since 2003. The number of surgeries has increased over the past few years, since robot-assisted lung resection of the right lobe became covered by health insurance in April 2018. In addition, lung segmentectomy is performed for lung metastases of malignant tumors in other organs. In deciding on the surgical approach, the increased technical difficulty of segmentectomy compared to lobectomy, owing to the anatomical complexity of the peripheral vessels and bronchi, needs to be considered, and novel surgical procedures and preoperative planning based on three-dimensional computed tomography( CT) images are necessary. We describe the preoperative management and surgical techniques used in approximately 250 lung segmentectomy procedures performed at our hospital up to May 2022, with no conversion to thoracotomy.

Number of lymph nodes dissected and upstaging rate of the N factor in robot-assisted thoracic surgery versus video-assisted thoracic surgery for patients with cN0 primary lung cancer.

PURPOSE: The accuracy of lymph node (LN) dissection in robotic surgery for lung cancer remains controversial. We compared the accuracy of LN dissection in robot-assisted thoracic surgery (RATS) vs. video-assisted thoracic surgery (VATS). METHODS: The subjects of this retrospective analysis were 226 patients with cN0 primary lung cancer who underwent robot-assisted or video-assisted thoracic lobectomy with LN dissection, in our department, between April, 2016 and February, 2021. We compared the numbers of all LNs and mediastinal LNs dissected, the time required for LN dissection, complications, and upstaging rates of the N factor between the groups. Furthermore, we performed an inverse probability of treatment weighting-adjusted analysis to reduce potential bias between the groups. RESULTS: The number of dissected LNs was higher in the RATS group in both the unweighted and weighted analyses. The time required for lymph node dissection was also longer in RATS. There was no significant difference in complications or in the upstaging rate of the N factor between the groups. CONCLUSION: More LNs were dissected with RATS. Thus, the usefulness of robot-assisted surgery for LN dissection needs to be investigated further.

[Thoracoscopic Superior and Subsuperior Segmentectomy of the Right Lower Lung for Lung Cancer].

The subsuperior segment (S*) is not frequently observed between the superior (S6) and posterior basal segments (S10). We present a case of video-assisted thoracoscopic surgery of S6+S* segmentectomy for a primary lung cancer patient. A 71-year-old man with a 20-mm nodule on the right S6, suspected of primary lung cancer( cT1bN0M0, stageⅠA2), was admitted to our hospital. Three-dimensional chest computed tomography (CT) revealed a subsuperior segmental bronchus (B*), originating from the common trunk of the lateral basal segmental bronchus( B9) and posterior basal segmental bronchus (B10). In order to obtain enough surgical margin, we performed S6+S* segmentectomy. The pathological diagnosis was invasive adenocarcinoma( pT1cN0M0, stageⅠA3). S* segmentectomy was considered to be useful method to ensure sufficient surgical margin when the lesion is in S* or in segments adjacent to it.

Causes and management of intraoperative complications in robot-assisted anatomical pulmonary resection for lung cancer.

Background: To perform safe robot-assisted anatomical lung resections, the details of intraoperative complications need to be shared among thoracic surgeons. However, only limited data are available. Methods: This retrospective, single-institutional study evaluated 134 patients who underwent robot-assisted anatomical lung resection. We examined the causes, management, and outcomes of all intraoperative complications. Results: Of the 134 eligible patients, 118 (88%) underwent lobectomy and 16 (12%) underwent segmentectomy. Intraoperative complications occurred in 17 (12.7%) patients. These complications included pulmonary artery (PA) injuries in seven patients, pulmonary vein (PV) injuries in three, azygos vein (AV) injury in one, superior vena cava (SVC) injury in one, bronchial injuries in three, and lung injuries in four. Most PA injuries were at a distal side and controlled by pressure, fibrin sealant, or stapling of the proximal side. In the three PV injuries, right upper PV was sandwiched by robotic instruments, V6 was punctured by the tip of the Maryland bipolar forceps, and the distal side of V2t was injured during tunneling of a minor interlobar fissure. These were controlled the same way as the PA injuries. The AV injury occurred during hilar lymph node (LN) dissection and was controlled by suturing. The SVC injury was caused by interference of the robotic forceps and the suction tube outside the field of view during upper mediastinal LN dissection. The injury was controlled by continuous pressure while layering polyglycolic acid sheets and fibrin glue. In the three bronchial injuries, B10 was injured during subcarinal LN dissection, right main bronchus was injured during upper bronchus dissection and the stapling failure of the bronchus occurred by strong traction. They were all repaired by suturing. All lung parenchymal injuries were caused by manipulation of robotic instruments outside the field of view. The lung injuries were repaired by suturing with pledgets. No cases were converted to thoracotomy. The 30-day mortality rate was 0.7%. The cause of mortality was pneumonia. Conclusions: In robot-assisted anatomical pulmonary resection for lung cancer, most major intraoperative complications can be safely managed robotically without conversion to thoracotomy.

Robotic single right anterior medial (S3b) subsegmentectomy for early primary lung cancer in a patient with a small physique.

Subsegmentectomy is an optional treatment for early primary lung cancer presenting without adequate surgical margins for wedge resection. There are no previous reports regarding a robotic single subsegmentectomy. We report a robotic single subsegmentectomy of the right anterior medial subsegment (S3b). The lung parenchyma was dissected with a Vessel Sealer Extend along the intersubsegmental veins for proper lung mobilization to solve the directional limitations of the robotic stapler. Additionally, we inserted the most ventral port from the subcostal region to increase the distance between the ports. Performing a robotic single subsegmentectomy is challenging. However, our techniques help to achieve a safe and effective operation.

Clinical effect of soft coagulation for air leak treatment during pulmonary lobectomy.

BACKGROUND: Soft coagulation using the VIO soft coagulation system is used to treat minor lung air leaks during pulmonary resection in Japan. We previously reported that it has a similar effect as the air leak treatment with fibrin glue. We evaluated the efficacy of soft coagulation using the VIO soft coagulation system for lung air leakage during pulmonary resection. METHODS: Intraoperative air leaks from the interlobar lung parenchyma were observed in 42 of the 283 patients who underwent video-assisted thoracoscopic surgery lobectomy between 2016 and 2018. We retrospectively reviewed these 42 patients who were treated using the VIO soft coagulation system for air leaks. We classified the air leaks in to grades using the Macchiarini scale score and evaluated the surgical outcomes of air leak treatment. RESULTS: Air leaks from the interlobar lung parenchyma having Macchiarini scale scores 1, 2, and 3 occurred in 8, 17, and 17 patients, respectively. In all the 8 patients with score 1 air leaks (100%), the air leaks could be controlled using the VIO soft coagulation system alone, and none had delayed pneumothorax requiring intervention. Of the score 2 and 3 air leaks, 52.9% and 35.3% were controlled using the VIO soft coagulation system alone, respectively. CONCLUSIONS: Macchiarini scale score 1 air leaks from the interlobar lung parenchyma could be well controlled using the VIO soft coagulation system. Therefore, soft coagulation with this system may be an alternative method for treating minor air leaks during pulmonary resection surgery.

[Simultaneous Resection of Mediastinal and Liver Hydatid Disease].

Cystic echinococcosis is an uncommon zoonosis in Japan. Typical location of the cyst is the liver and the lung. Mediastinal hydatidosis is found in less than 0.1% of all hydatid disease patients. We report a rare case of 68 years old male with mediastinal and liver hydatid cysts. Serological test confirmed the diagnosis of hydatidosis. The patient underwent complete resection of mediastinal and liver cysts successfully. Postoperative follow-up for two years has not shown any signs of recurrence. Simultaneous resection of the cysts in different sites including mediastinum is rare and has not been reported in Japan. Hydatid disease is an important differential diagnosis for patient who has cryptogenic liver cyst and history of contact to wildlife or unsterile water.

Robot-assisted and video-assisted thoracoscopic surgery for thymoma: comparison of the perioperative outcomes using inverse probability of treatment weighting method.

Background: Minimally invasive surgery is the standard treatment for early-stage thymoma. We compared the perioperative outcomes between robot-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) for thymoma. Methods: Between April 2011 and August 2021, patients with thymoma who underwent thymectomy by RATS (n=20) or VATS (n=37) at our hospital were retrospectively reviewed. We evaluated the postoperative quality of life (QOL), surgical outcomes, complications, mortality, and pain grade. Postoperative QOL was assessed according to the time to achieve "B duration" and "CIII duration" based on the Nursing Dependency Score and Nursing Criteria, respectively. Results: After the inverse probability of treatment weighting (IPTW), the B duration and CIII duration were significantly shorter with RATS than with VATS (P<0.001 and P=0.037, respectively). These superior results of RATS group compared to those of the VATS group were confirmed with logistic regression analysis (OR 0.25, 95% CI: 0.10-0.63, P=0.003; and OR 0.31, 95% CI: 0.12-0.76, P=0.011, respectively). After the IPTW, the VATS group had significantly fewer patients with epidural analgesia than the RATS group (P=0.018). In contrast, additional regular analgesics (including those for wound pain and neuralgia) were prescribed significantly more often during postoperative hospitalization in the VATS group (P=0.033). Patients in both groups had no myasthenic crisis or mortality. The postoperative pain grade at the first and second follow-ups did not significantly differ between the two groups after the IPTW (P=0.376 and P=0.109, respectively). Conclusions: RATS offered the advantages of improved postoperative QOL according to nursing care systems compared to VATS.

Robot-assisted vs. video-assisted thoracoscopic surgery in lung cancer.

Background: The major advantages of robot-assisted surgery are the fine field of view provided by the high-precision three-dimensional (3D) images and the good operability provided by the robotic arms that enables precise movements. A growing number of retrospective studies have compared robotic-assisted thoracoscopic surgery (RATS) with video-assisted thoracoscopic surgery (VATS), but the number of cases is limited and the results are contradictory. Methods: We studied the medical records of primary lung cancer patients who underwent lobectomy with lymph node dissection between 2017 and 2020. Four hundred and eleven patients fulfilled the inclusion criteria in this study (RATS: 103; VATS: 308). We compared the perioperative factors and postoperative results of the VATS and RATS groups. Further, we adjusted background factors using propensity score matching (PSM) then compared the results of 200 patients (100 patients in each group). In this study, we matched interlobar fissure completeness, which affects operative difficulty and operative time; however, this has been superficially compared in previous studies. Results: After PSM, a significant difference was observed in the intraoperative blood loss (RATS: 53.3 mL, VATS: 120.3 mL, P=0.04). The rates of surgical complications were comparable between the groups (10.0% vs. 13.0%, P=0.66) with similar mean operation times (RATS: 215.0 min, VATS: 210.1 min, P=0.57). The mean postoperative stay in the RATS group was shorter than that in the VATS group (10.0 vs. 11.5 days, P=0.04). Conclusions: Initial experience of RATS had no obvious drawbacks when compared with that of VATS on propensity-matched analysis.

Interlobar division using vessel-sealing system in robot-assisted pulmonary lobectomy.

Objective: We investigated the safety of a novel interlobar fissure division technique using the da Vinci vessel sealing system in robot-assisted pulmonary lobectomy. Methods: The medical records of patients who underwent robotic pulmonary lobectomy with node dissection for primary lung cancer between 2018 and 2020 were reviewed. The inclusion criteria were fulfilled by 111 patients, whose perioperative factors and postoperative results were compared with those previously reported. Furthermore, the new robotic lung interlobar division technique using the da Vinci vessel sealing system without a robotic stapler was evaluated in patients with low-grade incomplete fissure. We considered the Craig and Walker classification of lung fissures grades 1 and 2 as a good adaptation for the vessel sealing system interlobar fissure division. Results: The vessel sealing system group had shorter mean operative and console times (P = .03 and P = .01, respectively) and lesser median intraoperative blood loss (20 mL vs 50 mL; P = .01). The vessel sealing system group had lower surgical complication rates (2.2% vs 20.0%; P = .01). The incidence of persistent postoperative air leak was lower (0% vs 10.0%; P = .06), and fewer robotic stapler cartridges were used during surgery (3.4 vs 5.6; P < .001) in the vessel sealing system group than in the stapler group. Conclusions: We report the safety of using the da Vinci vessel sealing system as an alternative to the use of robotic staples for interlobar fissure division in robot-assisted pulmonary lobectomy. This technique seems easy and feasible though limited to the low-grade incomplete fissure.