[The Novel Procedure for Thoracoscopic Anatomical Segmentectomy].

Since 2004, over 300 patients have undergone thoracoscopic segmentectomy without mini-thoracotomy. Thoracoscopic segmentectomy is one of the most complicated surgeries. To perform the complex segmentectomies, pre-operative simulation and 3-dimensional multi-detector computed tomography( 3DCT) are both essential for safely performing operations and for securing adequate surgical margins. Comprehension of the intersegmental and intrasegmental veins to visualize the segmental border facilitates an easier parenchymal dissection. We describe our method and knack for creating an inflation-deflation line for lung segmentectomy that could especially be useful in thoracoscopic procedures for seg-mentectomy. The 5-year over overall survival, cancer specific survival and recurrence free survival rates were 91.8%( curative intent 98.1% versus compromised 74.6%), 100% and 98.1%( curative intent 100% versus compromised 93.3%). According to these technical aspects, our method of thoracoscopic segmentectomy is acceptable for selective patient.

Influx of air into the left atrium during lung resection.

OBJECTIVES: In this study, we aimed to determine conditions associated with the development of air bubbles in the pulmonary veins during lung resection. METHODS: A total of 28 patients who underwent lung resection at our institution between October 2016 and March 2018 were included in the study. An intraoperative transesophageal echocardiography was conducted, and the influx of air bubbles in the orifice of the pulmonary vein leading to the left atrium was observed during lung resection. RESULTS: The median age of all patients was 75 years. The study included 13 men and 15 women. Moreover, seven, 14, and seven patients underwent wedge resection, segmentectomy, and lobectomy, respectively. The presence of air bubbles was observed in 15 patients and was detected when the lung parenchyma was cut (13 patients) or compressed (3 patients) using staplers and when an energy device was used (1 patient). No postoperative organ infarction occurred in any patients. CONCLUSIONS: Although the presence of air bubbles was noted in the pulmonary vein during lung resection via transesophageal echocardiography, the clinical condition of the patients in our study did not deteriorate. The clinical significance of air bubbles is not clear. Therefore, more data about such events must be collected in future.

The preoperative assessment of subpleural lung cancer movement to distinguish thoracic wall adhesion or invasion using four-dimensional computed-tomography.

Four-dimensional computed tomography (4DCT) is a relatively new technology. A review of the relevant medical literature reveals only very limited previous investigations of the utility of this technique. We report two cases of lung cancer located adjacent to the pleura in which 4DCT was used to assess parietal pleural invasion or adhesion based on the differential movements of tumors. We performed 4DCT to determine the surgical approach after obtaining appropriate informed consent from the patient. Based on 4DCT, Patient 1 showed there was no adhesion and we could perform thoracoscopic right lower lobectomy and the final pathological diagnosis was pT1bN0M0. Patient 2 Based on 4DCT, showed suspicious of invasion or adhesion. we performed chest wall resection because of tumor invasion in the eighth and ninth costal bones; a final pathological diagnosis of pT3N0M0 was made.

Determination of the intersegmental plane using the slip-knot method.

BACKGROUND: Visualization of intersegmental planes in the lung is desirable for precise anatomical lung segmentectomy. We developed the slip-knot method for creating inflation-deflation lines. This study aimed to assess relevant data for thoracoscopic segmentectomy performed using this method. METHODS: In the slip-knot method, the objective segmental bronchus is looped with a monofilament thread. One end of the thread is then pulled during temporary bilateral ventilation, causing the knot to slip toward the bronchus. Thereafter, bronchial ligation is tightened to block the outflow of segmental air, ensuring that the segment remains expanded while the other reserved segments collapse on resumption of unilateral ventilation. Data from 221 patients who underwent thoracoscopic pulmonary segmentectomy between 2010 and 2016 were analyzed. RESULTS: A total of 147 patients (67%) were indicated for the slip-knot method, and 74 cases (33%) were non-adaptive cases. Ninety six percent of 147 cases were well adapted to the slip-knot method, which allowed us to obtain good inflation-deflation line images to determine the intersegmental plane. The mean operative time was 171±51 min (range, 71-367 min). The mean duration of chest tube insertion was 1.5±1.2 days (range, 1-7 days). Three cases (2.0%) had prolonged air-leakage and one (0.7%) case had readmission for late air-leakage. CONCLUSIONS: Our method enables determination of anatomical intersegmental planes using only one monofilament thread, thus facilitating thoracoscopic pulmonary anatomical segmentectomy.

[Present Status and Future Issues of Multidisciplinary Treatment of Lung Cancer from the Viewpoint of a Respiratory Surgeon].

With the advent of molecular targeted therapeutic agents and immunity checkpoint inhibitors, lung cancer drug therapy has advanced. We cannot expect to improve the performance of surgical treatment without drug therapy. The problem of improving the performance of surgical treatment for lung cancer is:① the role of surgery in multidisciplinary treatment for c-stageⅢ N2 lung cancer, ② post-operative adjuvant therapy, ③ multidisciplinary treatment of post-operative recurrence, ④ salvage surgery, and ⑤ sublobar resection in high risk cases. We will describe each of these with reference to our own experiences and literature considerations.

Pedicled gastric seromuscular patch for one-stage closure of a bronchopleural fistula: a case report.

BACKGROUND: One-stage closure and fenestration are the available surgical options for bronchopleural fistula (BPF). One-stage closure may be applicable in cases with favorable infection control. Closing the bronchopleural stump is difficult due to thick adhesion caused by inflammation and a high risk of pulmonary artery injury. We report the successful closure of a BPF using a gastric seromuscular patch with an omental pedicle flap. CASE PRESENTATION: A 73-year-old man underwent right lower lobectomy with ND2a-2 lymph node dissection for lung adenocarcinoma. He was admitted to a local hospital for pneumonia. Three days after admission, his thoracic cavity was drained and a BPF was suspected. During the primary operation, the latissimus dorsi muscle and anterior serratus muscle were dissected via posterolateral incision, and we decided to close the fistula using the gastric seromuscular layer and omental pedicle flap. The patient was discharged 20 days after surgery. After 2 years, he has not had cancer recurrence and currently leads an active life. CONCLUSIONS: This method provided immediate airtight closure and luminal opening of the middle bronchus in our patient with a large BPF and appeared superior to using the omentum alone. This procedure is useful for one-stage closure and does not require fenestration in cases with favorable infection control.

Hyperbaric oxygen therapy for postoperative ischemic bronchitis after resection of lung cancer.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) has been used successfully in the treatment of specific ischemic injuries, but has been a little evaluated specifically in postoperative ischemic bronchitis (POIB). The purpose of this study was to evaluate the effect of HBOT when used for POIB after resection of lung cancer. METHODS: From January 1999 to December 2016, 1,100 patients underwent lymph node dissection (LND) and either anatomic pulmonary resection or lung resection with bronchoplasty for lung cancer. POIB was diagnosed by bronchoscopy. HBOT was administered after POIB was diagnosed. HBOT comprised one 60-minute session daily in the hyperbaric chamber at 2.0 absolute atmospheres with 100% oxygen. We retrospectively analyzed the clinical course, timing of onset of POIB, outcomes, and any adverse events. RESULTS: Seven patients were identified to have had POIB treated with HBOT, all of whom were men with a smoking history and a median age of 65 years (range, 57-72 years). The operative procedures included three lung resections with bronchoplasty, three right lower lobectomies, and one right middle lobectomy performed owing to torsion of the middle lobe after right upper sleeve lobectomy. All 7 patients underwent subcarinal LND. POIB was diagnosed at a median of 11 days (range, 4-41 days) postoperatively. The median duration of an HBOT session was 7 days (range, 3-11 days). POIB resolved in 5 patients but worsened in 2, both of whom required further surgery. CONCLUSIONS: Prospective clinical trials are now needed to confirm the potential benefits of HBOT in POIB.

[Successful Early Surgical Treatment for Infected Traumatic Pulmonary Pseudocyst].

Almost all traumatic pulmonary pseudocysts (TPP), such as cavitary pulmonary lesions after blunt chest trauma, resolve spontaneously. On the contrary, secondary infection of a TPP should be considered in the presence of purulent sputum or hemosputum and a persistent cavity. We report a case of an infected TPP that was successfully treated by early surgical treatment. A 25-year-old man was transferred to our hospital with a TPP, shown by computed tomography (CT) as having a thick-walled large cavity, after the acute phase of blunt chest trauma. Purulent hemosputum suggested infection of the cavity. Serial CT scans of the chest revealed a persistent cavity. The thick-walled large cavity was diagnosed as a secondary infection of the TPP, that is, a potential lung abscess. We resected the cavity before a systemic inflammatory reaction occurred.

Port-access thoracoscopic bisubsegmentectomy of right upper lobe posterior and anterior segments.

A 64-year-old woman was admitted to our hospital with a 16-mm non-solid tumor with pure ground-glass nodule (GGN) contents in the posterior segment near the anterior segment of her right upper lung lobe that was suspicious of adenocarcinoma in situ (AIS). Three-dimensional computed tomography (3DCT) simulation was performed to identify the subsegmental artery and vein pre- or intra-operatively. Port-access thoracoscopic bisubsegmentectomy of the right upper lobe was performed. A frozen section revealed AIS. The tumor size was 13 mm and the surgical margin from the tumor edge to cutting line was more than 20 mm. The surgical time was 191 minutes and bleeding was 101 mL. The chest tube duration was 3 days and the post-operative hospital stay was 6 days.

Thoracoscopic left S4a subsegmentectomy.

A 63-year-old woman who underwent a left hepatic lobectomy for hilar cholangiocarcinoma was referred to our department for further management. Chest computed tomography showed a lung nodule that was increased in size to 8 mm in the S4a. The differential diagnosis was metastasis versus primary lung cancer. Thoracoscopic left S4a subsegmentectomy was performed. The operative time was 158 min. The blood loss was minimal. Air leakage was not observed, and a chest tube was removed on POD 1. The patient was discharged home on POD 3. The final diagnosis was primary lung cancer (T1aN0M0 stage IA). Surgical margin was 2.0 cm.

Thoracoscopic wedge resection and segmentectomy for small-sized pulmonary nodules.

With the recent increase in the detection of small-sized lung nodules because of the widespread use of computed tomography (CT), limited resection and minimally invasive surgery are preferred by patients with these lesions. In particular, the detection of nodules that show ground-glass opacity during high-resolution CT has increased. Although lobectomy and lymph node dissection were the standard procedures used for treating lung cancer, limited wedge resection and segmentectomy have become acceptable for treating small-sized lung cancers with nodules showing ground-glass opacity. These limited procedures are widely performed, especially because they can be accomplished thoracoscopically. Furthermore, not only simple segmentectomy but also complex segmentectomy and subsegmentectomy can be performed using three-dimensional (3D)-CT to achieve sufficient resection based on tumor size. There are, however, technical difficulties in thoracoscopic wedge resection and segmentectomy. While it may be curative for small-sized lung nodules, it is sometimes difficult to correctly perform wedge resection when the tumor is not identified intraoperatively. In such cases, we usually perform tumor marking before operating. However, serious complications, such as cerebral air embolism, have been reported. Further, although it can sufficiently resect small-sized lung nodules, segmentectomy is more technically complex than wedge resection. Therefore, we have developed methods to overcome these technical difficulties. By using a hookwire method in a hybrid operating room and 3D-CT simulation for each wedge resection and segmentectomy, we have obtained good outcomes. Limited resection individualized for each patient will continue to evolve with applications such as CT.

Swine model for training surgeons in minimally invasive anatomic lung segmentectomy.

BACKGROUND: Despite the increasing demand for thoracoscopic lung segmentectomy, the appropriate training method is not well established. Therefore, we developed a swine model for anatomical thoracoscopic lung segmentectomy training. METHODS: Three-month-old pigs, weighing 40 to 45 kg, were used in this model. Anterior segmentectomy of the left cranial lobe and segmentectomy of the most anterior left caudal lobe were performed under general anesthesia and differential ventilation. Participants from several institutions participated in this program, which included training lectures and surgical skill drills. RESULTS: From 2010 to 2015, 33 pigs were used for the lung segmentectomy training with 51 trainees. Eight pigs were operated on using the hybrid approach, and 25 pigs were operated on using the complete thoracoscopic approach. Among 25 pigs in which the complete thoracoscopic approach was used, conversion to thoracotomy was required in 3 pigs, owing to hemorrhage in two and failure of differential ventilation in one. The no-touch method in supine position provided sufficient intersegmental delineation of 20 (76%) planes among 26 left anterior segmentectomies in the cranial lobe. CONCLUSIONS: Our live swine model of anatomical thoracoscopic lung segmentectomy is considered a good choice for training surgeons on how to perform minimally invasive lung segmentectomy in humans.

How to demarcate intersegmental plane with resected-segments inflation method using the slip knot technique in thoracoscopic anatomic segmentectomy.

Intersegmental demarcation line on the surface of the visceral pleura could not be found at thoracoscopic findings. The resected segments inflation (RSI) method has been reported as a useful technique for visualizing the intersegmental demarcation line during segmentectomy. Thoracoscopic anatomic segmentectomy is performed as follows: firstly, the pulmonary vein and artery of the segment planned for resection are dissected from the hilum in order to isolate the segmental bronchus located behind the pulmonary artery. Secondly, a monofilament non-absorbable suture is passed through the segmental bronchus, and a slip-knot is made outside the thorax. Thirdly, bilateral lung ventilation with pure oxygen is conducted. When the affected segment has inflated sufficiently, the slip knot suture is pulled and the segmental bronchus is ligated and collapse of the lung is made on reserved segments. Fourthly, as inflation of the affected segment and collapse of the reserved segments could be found, resection of intersegmental plane could be easily performed with the inflation-deflation line and the intersegmental pulmonary vein. If resected segmental bronchus could be identified, thoracoscopic segmentectomy with the slip-knot technique would be applicable. This slip-knot procedure is economical and is not need special instrument.

Posterior approach to thoracoscopic pulmonary segmentectomy of the dorsal basal segment: A single-institute retrospective review.

OBJECTIVE: Anatomic resection of the dorsal area of the basal segment of the lower lobe is difficult because of the deep location of vessels and bronchi in the parenchyma. This study aimed to describe a novel technique for port-access thoracoscopic segmentectomy of the dorsal (S10) and lateral dorsal segments (S9+10). METHODS: This retrospective study analyzed 20 patients who underwent S10 and S9+10 thoracoscopic segmentectomy via a posterior approach between January 2004 and March 2016. In this approach, the lung parenchyma between S6 and S10 was divided along V6b,c from the dorsal side of the lower lobe, which exposed the targeted bronchus (B10, B9+10) and artery (A10, A9+10) and enabled anatomic S10 and S9+10 segmentectomy. RESULTS: Of the 20 patients, 15 had lung cancer, 3 had metastases, and 2 had benign nodules. The number of segmentectomies of the right S10, right S9+10, left S10, and left S9+10 was 5, 5, 1, and 9, respectively. Median operative time was 165 minutes (range, 107-276 minutes). The median duration of chest tube insertion was 1 day (range, 1-2 days). One patient had atelectasis. Median hospital stay was 6 days (range, 3-11 postoperative days). No recurrence or mortality was observed during the median follow-up period of 46 months. CONCLUSIONS: The posterior approach for port-access thoracoscopic segmentectomy at S10 or S9+10 is technically challenging, but in our hands it has been feasible. It exposes the targeted bronchus (B10, B9+10) and artery (A10, A9+10) and enables anatomic S10 and S9+10 segmentectomy while avoiding inessential parenchymal splitting from the major fissure.

Thoracoscopic anatomical lung segmentectomy using 3D computed tomography simulation without tumour markings for non-palpable and non-visualized small lung nodules.

OBJECTIVES: Although wedge resection can be curative for small lung tumours, tumour marking is sometimes required for resection of non-palpable or visually undetectable lung nodules as a method for identification of tumours. Tumour marking sometimes fails and occasionally causes serious complications. We have performed many thoracoscopic segmentectomies using 3D computed tomography simulation for undetectable small lung tumours without any tumour markings. The aim of this study was to investigate whether thoracoscopic segmentectomy planned with 3D computed tomography simulation could precisely remove non-palpable and visually undetectable tumours. METHODS: Between January 2012 and March 2016, 58 patients underwent thoracoscopic segmentectomy using 3D computed tomography simulation for non-palpable, visually undetectable tumours. Surgical outcomes were evaluated. RESULTS: A total of 35, 14 and 9 patients underwent segmentectomy, subsegmentectomy and segmentectomy combined with adjacent subsegmentectomy, respectively. All tumours were correctly resected without tumour marking. The median tumour size and distance from the visceral pleura was 14 ± 5.2 mm (range 5-27 mm) and 11.6 mm (range 1-38.8 mm), respectively. Median values related to the procedures were operative time, 176 min (range 83-370 min); blood loss, 43 ml (range 0-419 ml); duration of chest tube placement, 1 day (range 1-8 days); and postoperative hospital stay, 5 days (range 3-12 days). Two cases were converted to open thoracotomy due to bleeding. Three cases required pleurodesis for pleural fistula. No recurrences occurred during the mean follow-up period of 44.4 months (range 5-53 months). CONCLUSIONS: Thoracoscopic segmentectomy using 3D computed tomography simulation was feasible and could be performed to resect undetectable tumours with no tumour markings.

Video-assisted thoracoscopic subsegmentectomy for small-sized pulmonary nodules.

Segmentectomy has been widely performed as one of the types of limited resections that are performed for the resection of small-sized lung nodules. Video-assisted thoracoscopic surgery has also been in demand as a minimally invasive surgery. Subsegmentectomy is a much more limited resection than segmentectomy, but the technique is complex because it requires keen anatomical identification of small pulmonary structures. Therefore, there has been little reported about subsegmentectomy in medical literature. The recent development of computed tomography is remarkable, and some reports describe three-dimensional computed tomography as providing useful information because it assists surgeons in the performance of thoracoscopic anatomical subsegmentectomy. The creation of an intersubsegmental line is a key process in subsegmentectomy, therefore, some methods have been reported. We have safely and accurately performed some video-assisted thoracoscopic subsegmentectomies for small-sized lung tumors, using the three-dimensional computed tomography simulation and creating the intersubsegmental line with the inflation-deflation technique. In this article, we describe the recent techniques and roles of video-assisted thoracoscopic subsegmentectomy, and offer prospects for this procedure with our clinical data.

Rho-Associated Protein Kinase (ROCK) Inhibitors Inhibit Survivin Expression and Sensitize Pancreatic Cancer Stem Cells to Gemcitabine.

BACKGROUND: Targeting pathways regulating survivin expression, which has been implicated in multidrug resistance of cancer cells, is a promising strategy to overcome cancer chemoresistance. To date, the role of rho-associated protein kinases (ROCKs) in survivin expression remains largely unknown. MATERIALS AND METHODS: The effects of ROCK inhibitors Y-27632 and fasudil on survivin expression and cell viability were determined by immunoblot analysis and dye exclusion, respectively, in PANC-1 CSLC, a cancer stem cell line derived from a serum-cultured, gemcitabine-sensitive pancreatic cancer cell line, PANC-1. RESULTS: siRNA-mediated knockdown of survivin revealed that the gemcitabine resistance of PANC-1 CSLC was dependent on survivin expression. Both Y-27632 and fasudil, reduced survivin expression in PANC-1 CSLC cells and sensitized them to gemcitabine. ROCK inhibition also reduced survivin expression in various other human cancer cell lines. CONCLUSION: Small molecule inhibitor-mediated targeting of ROCK may be a viable strategy to overcome cancer chemoresistance through down-regulation of survivin.

Aripiprazole, an Antipsychotic and Partial Dopamine Agonist, Inhibits Cancer Stem Cells and Reverses Chemoresistance.

BACKGROUND: There is a growing interest in repurposing antipsychotic dopamine antagonists for cancer treatment; however, antipsychotics are often associated with an increased risk of fatal events. The anticancer activities of aripiprazole, an antipsychotic drug with partial dopamine agonist activity and an excellent safety profile, remain unknown. MATERIALS AND METHODS: The effects of aripiprazole alone or in combination with chemotherapeutic agents on the growth, sphere-forming ability and stem cell/differentiation/chemoresistance marker expression of cancer stem cells, serum-cultured cancer cells from which they were derived, and normal cells were examined. RESULTS: At concentrations non-toxic to normal cells, aripiprazole inhibited the growth of serum-cultured cancer cells and cancer stem cells. Furthermore, aripiprazole induced differentiation and inhibited sphere formation, as well as stem cell marker expression of cancer stem cells while inhibiting their survivin expression and sensitizing them to chemotherapeutic agents. CONCLUSION: Repurposing aripiprazole as an anticancer stem cell drug may merit further consideration.

Impact of H3K27 Demethylase Inhibitor GSKJ4 on NSCLC Cells Alone and in Combination with Metformin.

BACKGROUND: GSKJ4, an H3K27 demethylase inhibitor, reportedly exhibits antitumor activity against specific cancers harboring genetic alterations in genes encoding chromatin modulators. However, its potential as an anticancer agent against human cancers not associated with such genetic alterations, including non-small cell lung cancer (NSCLC), remains unknown. MATERIALS AND METHODS: The effect of GSKJ4 on the growth of three NSCLC cell lines and normal lung fibroblasts was investigated using the WST-8, dye exclusion, and colony formation assays. RESULTS: GSKJ4, alone and in combination with an anti-diabetic drug metformin, induced cell death and inhibited the growth of NSCLC cell lines efficiently at concentrations non-toxic to normal cells, irrespective of their genetic backgrounds (mutations in the KRAS, TP53 and EGFR genes) and also of their resistance to cisplatin and paclitaxel. CONCLUSION: GSKJ4, being a promising anticancer agent for NSCLC, may be effective against a wider spectrum of cancers than previously thought.