Dual Image Navigation to Secure Surgical Margins in Thoracoscopic Segmentectomy.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) segmentectomy is being increasingly used for the management of non-small cell lung cancer. For non-palpable lesions, surgeons frequently find difficulty in ensuring a sufficient surgical resection margin. OBJECTIVE: The purpose of this study was to evaluate the role of intraoperative dual image navigation in combination with the infrared thoracoscopy with intravenous injection of indocyanine green (IRT-ICG) method and intraoperative computed tomography (CT) in detecting oncological margins. METHODS: This study involved 34 consecutive patients who underwent both IRT-ICG and intraoperative CT-assisted thoracoscopic segmentectomy between October 2017 and July 2021. The intersegmental line on the visceral pleura was visualized using the IRT-ICG method. The intersegmental line was marked by clipping, and an intraoperative CT scan was performed under bilateral lung ventilation. Intraoperative CT or three-dimensional CT reconstruction images were used by surgeons to confirm the correct anatomic segmental border and to secure a sufficient resection margin. RESULTS: A well-defined intersegmental line was observed in 91.2% of patients. In eight cases, the surgeon needed to make some modifications to the resection line to secure a sufficient surgical margin. The mean surgical margin assessed on gross examination by the pathologist was 23.4 ± 9.0 mm. Complete resection was achieved in all patients using this approach. CONCLUSIONS: Intraoperative dual image navigation combined with the IRT-ICG method and intraoperative CT scan enables surgeons to perform definitive VATS segmentectomy for non-palpable lesions.

Regeneration of emphysematous lungs using gelatin sheets that release basic fibroblast growth factor.

PURPOSE: Basic fibroblast growth factor (bFGF) induces regeneration and neovascularization of the lungs. We conducted this study to demonstrate the regeneration of emphysematous lungs achieved by gelatin sheets that slowly release bFGF into the visceral pleura in a canine model. METHODS: Porcine pancreatic elastase was used to induce bilateral lower lobe pulmonary emphysema in dogs. Slow-release bFGF gelatin sheets were attached to the visceral pleura of the left lower lobe via thoracotomy. The subjects were divided into two groups: one treated with gelatin sheets containing slow-release bFGF (bFGF+ group, n = 5), and the other, treated with only gelatin sheets (bFGF- group, n = 5). The subjects were euthanized after 28 days and histologic lung assessment was performed. The results were evaluated in terms of the mean linear intercept (MLI) and microvessel count. RESULTS: The MLI was significantly shorter in the bFGF+ group than in the bFGF- group; (110.0 ± 24.38 vs. 208.9 ± 33.08 µm; P = 0.0006). The microvessel count was not significantly different between the bFGF+ and bFGF- groups (12.20 ± 3.007 vs. 5.35 ± 2.3425; P = 0.075); however, it was significantly higher in the bFGF-attached lungs than in the emphysema group (12.20 ± 3.007 vs. 4.57 ± 0.8896; P = 0.012). CONCLUSIONS: Attaching gelatin sheets with slow-release bFGF to the visceral pleura induced lung regeneration and vascularization in a canine pulmonary emphysema model.

Safe pneumonectomy for locally advanced lung cancer after induction therapy.

PURPOSE: To assess the safety and long-term outcomes of pneumonectomy after IT (IT-Pn) versus upfront pneumonectomy without IT (U-Pn) for locally advanced non-small-cell lung cancer (NSCLC). METHODS: We reviewed the clinical records of 69 patients who underwent pneumonectomy as U-Pn (n = 30) or IT-Pn (n = 39) between 2000 and 2019 at our institution, RESULTS: U-Pn included patients with pathological N0 (n = 13), N1 (n = 11) and N2 (n = 6). Among the patients treated with IT-Pn, 18 had pathological N0 (including 7 with complete responses), 5 had N1, 14 had N2, and 2 had N3. It was suggested that 22 cases could be down-staged after IT. The 5-year overall survival (OS) was 28.1% in the U-Pn group and 43.1% in the IT-Pn group (p = 0.275), being 40.2% for IT-Pn with p-N2,3, but not reached for U-Pn with N2 (p = 0.307). The 90-day mortality was 6.7% for the U-Pn group and 5.1% for the IT-Pn group (p = 0.646). Major complications occurred in 25 patients (64.1%) treated with IT-Pn and 18 patients treated with U-Pn (60.0%; p = 0.602). CONCLUSIONS: Pneumonectomy for NSCLC can be performed safely after IT with favorable results. For patients with N2 disease, induction therapy followed by surgery may warrant further study.

Role of surgery in multi-modality treatment for carcinomatous pleuritis in patients with non-small cell lung cancer.

OBJECTIVE: To evaluate the role of surgery in the treatment of the patients with non-small cell lung cancer with pleural dissemination. METHODS: The clinical records of 25 patients (mean age 69 years) diagnosed with carcinomatous pleuritis during a thoracotomy by pathological examination and followed by surgery between 1994 and 2012 were reviewed. The treatment modality, including surgery, the clinicopathologic characteristics and 5-year survival were analyzed. RESULTS: There were 16 adenocarcinomas, 6 squamous cell carcinomas and 3 large cell carcinomas. Surgery included resection of the main tumor by partial resection in 10 cases, segmentectomy in 2 cases, lobar resection in 12 cases and bilobectomy in 1 case. Intrathoracic irrigation was performed in 20 cases. The pathological N status was N0/N1/N2/Nx: 10/6/7/2. Fifteen patients received adjuvant therapy. The overall 5-year survival rate was 22.2 %. The 5-year survival rates of the N0, N1 and N2 groups were 36.0, 16.7 and 14.3 %, respectively (p = 0.0068). Nine patients lived more than 3 years including 5 in N0, 3 in N1 and 1 in N2. CONCLUSIONS: Surgery should not be excluded from the multi-modality treatment of patients with carcinomatous pleuritis because there are some patients who could benefit from surgery especially if they are in N0 status.

[Pulmonary Metastasis from a Phyllodes Tumor of the Breast Developing Sixteen Years after Initial Surgery].

We report a case of solitary pulmonary metastasis from a phyllodes tumor of the breast appearing 16 years after initial surgery. The patient was a 56-year-old woman who had undergone surgical extirpation of a left breast tumor diagnosed as phyllodes tumor (borderline malignancy) in 1998, and a right breast tumor diagnosed as fibromatosis in 2000. Sixteen years after the initial operation, she consulted our hospital because of a chest X-ray abnormality detected at a screening examination. Chest computed tomography revealed a well defined nodular shadow in the left upper lobe of the lung. Surgery was done since primary lung cancer was suspected. However, pathological diagnosis was a pulmonary metastasis from the phyllodes tumor of the left breast. Right breast tumor was also diagnosed as a metastasis from the left breast tumor by histopathological re-evaluation.

Novel therapeutic approach for pulmonary emphysema using gelatin microspheres releasing basic fibroblast growth factor in a canine model.

PURPOSES: The prognosis of patients with emphysema is poor as there is no truly effective treatment. Our previous study showed that the alveolar space was smaller and the microvessel density was higher in a canine emphysema model after the intrapulmonary arterial administration of gelatin microspheres slowly releasing basic fibroblast growth factor (bFGF-GMS). In the present study, we evaluated the functional effect of injecting bFGF-GMS via the pulmonary artery in this canine pulmonary emphysema model. METHODS: Using the porcine pancreatic elastase (PPE)-induced total emphysema model, we approximated the value of lung compliance with a Power Lab System, and performed blood gas analysis in a control group, a total emphysema group, and a bFGF group in which bFGF-GMS were injected toward the whole pulmonary artery via the femoral vein. Each group comprised five dogs. RESULTS: Lung compliance was higher in the total emphysema group than in the control group (p = 0.031), and the bFGF group showed no significant improvement of lung compliance vs. the total emphysema group (p = 0.112). PaO2 (partial pressure of oxygen in arterial blood) was improved by administering bFGF-GMS in the total emphysema model (p = 0.027). CONCLUSION: In the canine total emphysema model, blood gas parameters were improved by the whole pulmonary arterial administration of bFGF-GMS. This method has the potential to be an effective novel therapy for pulmonary emphysema.

Recurrence-free survival curve for pulmonary metastasectomy in colorectal cancer plateaus at 3 years.

Pulmonary metastasectomy in colorectal cancer (CRC) has encouraging results; however, specific criteria for lung resection and the timing of resection remain undetermined. Therefore, in this study, we aimed to examine the long-term prognosis and 10-year survival rates and analyze poor prognostic factors in patients who underwent resection of pulmonary metastases from CRC. This retrospective, single-institution study included 156 patients with controlled primary CRC and metastases confined to the lungs or liver who underwent pulmonary metastasectomy between 2005 and 2022. Statistical analyses were conducted using the X2 and two-tailed Student's t test to compare variables. The receiver operating characteristic (ROC) curve was used to determine the appropriate cut-off point for tumor size as a predictive factor of survival. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and non-parametric group comparisons were performed using log-rank tests. The 5- and 10-year OS rates were 67% and 59%, respectively. Further, there was no recurrence 38 months post-surgery, and the RFS curve plateaued. Moreover, by 88 months post-surgery, no deaths occurred, and the OS curve plateaued. Multivariate analysis revealed that a pulmonary metastatic tumor >14 mm and disease-free interval <2 years indicated poor prognosis. The RFS curve for pulmonary metastasectomy may plateau approximately 3 years after surgery. Pulmonary metastasectomy can achieve long-term survival in selected patients with CRC. Furthermore, surgical resection of recurrence after pulmonary metastasectomy may lead to better results. Thus, tumor size and disease-free interval may be independent prognostic factors.

Tracheal repair with sternocleidomastoid flap in mediastinoscopic surgery for esophageal cancer.

Tracheal injury during mediastinoscopic esophagectomy is a life-threatening complication that is challenging to manage. However, no precise treatment has been defined. An 80-year-old male patient with upper esophageal cancer underwent a mediastinoscopic esophagectomy and gastric tube reconstruction through the posterior mediastinal route. When the esophagus was separated from the trachea using a bipolar vessel sealing system, the left side of the membranous trachea incurred a 3-cm defect 7 cm below the sternal notch. We successfully repaired the tracheal injury not by directly suturing the defect but by reinforcing it with a pedicle sternocleidomastoid flap. The gastric tube was placed over the tracheal repair for esophageal reconstruction via a posterior mediastinal route. As a result, the patient recovered well and was discharged. A sternocleidomastoid flap might be another surgical option for reinforcement flaps in tracheal injuries.

[Mucosa-associated lymphoid tissue (MALT) lymphoma of the lung treated by surgery and rituximab; report of a case].

We report a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the lung treated by surgery and rituximab. A 47-year-old man was referred to our hospital because of the lesion in the right middle lobe, which had enlarged gradually. Chest computed tomography(CT) scanning showed an infiltrative shadow of the right middle lobe. He underwent right middle lobectomy for the MALT lymphoma whose diagnosis and treatment. The tumor was pathologically diagnosed as CD20 immunostaining was positive and the adjuvant treatment by rituximab was performed.

[Predictor of intrathoracic lymph node metastasis in peripheral non-small cell lung cancers 20 mm or less in greatest dimension].

PURPOSES: To assess the independent predictor of lymph node metastasis( LNM) in peripheral smallsized non-small cell lung cancers (NSCLCs), we conducted a clinicopathologic analysis of patients with small-sized NSCLCs with and without intrathoracic LNM. METHODS: We retrospectively studied 213 patients who had undergone surgical resection of NSCLCs 20 mm or less in diameter. Categories of patient characteristics were divided into 2 groups based on clinicopathologic features, and the incidence of LNM was compared. Univariate and multivariate analyses of factors affecting overall survival( OS) were also conducted. RESULTS: In pN1-2 group (n=19), the incidence of elevated (>5 ng/dl) of preoperative carcinoembryonic antigen (CEA) and larger tumor size (>10 mm) was significantly higher than that in pN0 group (n=194) [p=0.0004, 0.0025]. Preoperatively, 73.7% patients were diagnosed as having lower stage in N-staging. Multivariate analysis identified only pN staging as an independent prognostic factor (p=0.002). CONCLUSIONS: It is likely that preoperative CEA and tumor size are useful in selecting patients with micro-N1-2 disease among those with small-sized NSCLCs. Our results indicate that limited resection should be avoided in patients with elevated CEA or tumors more than 10 mm in size, even if preoperative radiographic findings suggest no intrathoracic LNM.

A New Method to Identify Air Leaks After Pulmonary Resection Using Indocyanine Green Aerosol.

BACKGROUND: This study investigated whether air leak sites resulting from pulmonary resection could be identified by the administration of aerosolized indocyanine green into the airway. METHODS: Sixty-one patients who underwent lung resection surgery (54 video-assisted thoracoscopic surgeries and 7 thoracotomies) during 2019 to 2021 were enrolled. An additional sealing test including indocyanine green administration and observation with a near-infrared camera was performed after the conventional sealing test. The results of the indocyanine sealing test were compared with those of the conventional sealing test and evaluated. The observation period set for evaluating adverse events was 1 month. RESULTS: The conventional sealing test detected 38 air leak points, of which 20 were caused by stapler-related pleural defects. The indocyanine green sealing test identified 55 indocyanine green fluorescent sites. Among these, 37 sites were matched with air leak points identified in the conventional sealing test, and 18 new sites were identified in the indocyanine green test. Reexamination of newly identified indocyanine green fluorescent sites with the conventional sealing test showed 13 air leak sites additionally. The detection rate of the conventional sealing test was 75% and that of the indocyanine green sealing test was 98% (P = .001). No complications attributable to the aerosolized indocyanine green were encountered. CONCLUSIONS: The indocyanine green sealing test could identify air leak points overlooked by the conventional method. This procedure may be suitable in video-assisted surgery to improve surgical field visibility, and it allows prolonged observation of the lung in a collapsed state.

[Prognosis of surgically treated large cell neuroendocrine carcinoma].

Large cell neuroendocrine carcinoma (LCNEC) is a relatively rare tumor in malignant lung neoplasms. The prognosis of LCNEC is poor and there is no consensus on the treatment for LCNEC. We report our retrospective assessment of 11 patients of LCNEC from 1999 to 2008. Three of 11 patients had malignant exudate at thoracotomy. Seven patients received limited resection. There was a recurrence even after complete surgical resection in its early stage. Four patients received platinum-based chemotherapy for adjuvant therapy or recurrence. The response to platinum-based chemotherapy was relatively good and may be comparable to that of small cell lung cancer. The overall 5-year survival rate was 30.3%. Pulmonary LCNEC represents an aggressive tumor and multimodal treatment is required.

Constant-rate intravenous infusion of indocyanine green leading to high fluorescence intensity in infrared thoracoscopic segmentectomy.

OBJECTIVES: The purpose of this study was to determine whether or not fluorescence could be increased by administering indocyanine green at a constant rate, thus stabilizing its blood concentration. METHODS: In 20 consecutive patients undergoing segmentectomy, the dominant pulmonary arteries were ligated, blocking blood in the target segment. Fluorescence intensity was then observed using different indocyanine green administration methods under infrared thoracoscopy. Intravenous administration of indocyanine green, via a syringe pump at a rate of 12.5 mg/min, was defined as the constant rate group. The bolus group was defined by a 5-mg indocyanine green rapid intravenous injection. The fluorescence intensity was compared at the time of maximum fluorescence and 2 minutes after fluorescence initiation. RESULTS: At maximum staining, the fluorescence intensity of the normal blood flow area was brighter in the constant rate group (median, 184.2; interquartile range, 170.2-200.1) compared with the bolus group (median, 122.3; interquartile range, 87.3-144.7; P = .0003). The fluorescence of the normal blood flow was retained even after 2 minutes. There was no difference in the fluorescence intensity of the ischemic segments. CONCLUSIONS: The constant rate method showed brighter and better fluorescence than the bolus injection, without an increase in the dose. The contrast between adjacent segments was clear, facilitating the differentiation of the areas.

Inhibition of Cell-surface Molecular GPR87 With GPR87-suppressing Adenoviral Vector Disturb Tumor Proliferation in Lung Cancer Cells.

BACKGROUND/AIM: GPR87 is a member of the cell surface molecular G protein-coupled receptors (GPCR) family and suggested to contribute to the viability of human tumor cells. Its tumor-specific expression and cell surface location make it a potential molecule for targeted therapy. In the present study, we aimed to examine the effect of silencing GPR87 expression and explore the possibility of establishing gene therapy against GPR87-overexpressing lung cancer. MATERIALS AND METHODS: Twenty malignant cell lines were investigated and GPR87-overexpressing H358 and PC9 lung cancer cells were subjected to inhibiting experiments. A short hairpin siRNA targeting the GPR87 gene was transformed into an adenoviral vector (Ad-shGPR87). Real-time RT-PCR and western blot analyses were performed to evaluate gene and protein expression. Tumors derived from human H358 cells were subcutaneously implanted in nude mice for in vivo experiments. RESULTS AND CONCLUSION: About 50% (10/20) malignant cells showed GPR87-overexpression, especially for lung cancer cells (70%, 7/10). Ad-shGPR87 effectively down-regulated the GPR87 expression, and significantly inhibited the cell proliferation in GPR87-overexpressing H358 and PC9 cells. Treatment with Ad-shGPR87 exerted a significant antitumor effect against the GPR87-expressing H358 xenografts. In addition, the gene expression of H3.3, a recently proved activator for GPR87 transcription, was positively correlated with GPR87 gene expression. Furthermore, a significant decrease of KRAS and c-Myc expression was observed in both cell lines after Ad-shGPR87 infection. In conclusion, GPR87 may play a critical role in cancer cell proliferation, and indicate its potential as a novel target for lung cancer treatment.

Anomalous right upper lobe pulmonary veins draining posterior to the pulmonary artery.

The anatomy of pulmonary vessels varies. The right upper pulmonary vein usually drains in front of the pulmonary artery to the left atrium. We herein describe a case of the right upper lobe pulmonary vein draining posterior to the pulmonary artery and absent right upper lobe pulmonary vein in the ventral hilum. A 64-year-old woman suspected to have lung cancer and scheduled for surgery underwent pre-operative three-dimensional computed tomography (3D-CT), which revealed that pulmonary vessels V1 + 3 and V2 drain posteriorly to the pulmonary artery. Video-assisted right upper lobectomy was performed because the patient was diagnosed with lung adenocarcinoma through intraoperative pathologic analysis, and all the pulmonary vessels were identified correctly during the operation. Despite the limited surgical field of video-assisted lobectomy, the operation was performed safely because the pre-operative 3D-CT assessment revealed the anatomy of the anomalous pulmonary vessels, helping us avoid missing any anomaly and vessel injury.

Lymphatic invasion is a cause of local recurrence after wedge resection of primary lung cancer.

OBJECTIVE: After securing a sufficient surgical margin at wedge resection and finding no pathologic evidence of residual tumor at the surgical margin, a considerable number of patients develop local recurrence. We investigated the correlation between sub-pleural lymphatic flow and local recurrence. METHODS: We retrospectively reviewed the medical records of 144 non-small cell lung cancer patients who underwent wedge resection between January 2006 and December 2014 at our institution. RESULTS: Postoperative recurrence was observed in 36 patients (25%). Of these, local recurrence was observed in 29 patients (80.5%). The proportion of all recurrence and local recurrence were significantly higher among patients with lymphatic vessel invasion (LVI) (p < 0.0001). Recurrence-free survival rate was significantly lower in patients with LVI (24.8%) than in patients without LVI (80.2%, p < 0.0001). Multivariate logistic regression analysis demonstrated LVI (odds ratio = 6.420, p = 0.0009) as a significant predictor of local recurrence. CONCLUSIONS: Intratumoral lymphatic invasion represents a major cause of local recurrence. Although we should aim for radical surgery whenever possible, when limited surgery is the only option, postoperative adjuvant treatment may need to be considered for patients showing lymphatic invasion even at an early stage.

Intraoperative Computed Tomography Navigation During Thoracoscopic Segmentectomy for Small-sized Lung Tumors.

Performance of thoracoscopic pulmonary segmentectomy for primary lung cancer or pulmonary metastases has recently increased. In patients with emphysema, identification of the intersegmental line is often difficult. For nonpalpable lesions, securing a sufficient surgical margin is more likely to be uncertain. The purpose of this study was to evaluate the efficacy of intraoperative computed tomography (CT) scan during video-assisted thoracoscopic surgery (VATS) pulmonary segmentectomy. This study included 12 patients who underwent intraoperative CT-assisted VATS segmentectomy between January 2015 and August 2016. After dividing the corresponding vessels and bronchi, the intersegmental line was marked by clipping, and intraoperative CT scan was performed under bilateral lung ventilation. The intraoperative CT or 3-dimensional CT reconstruction images were used by the surgeons to confirm the correct anatomical segmental border and to secure a sufficient resection margin. In all patients, the location of the lesions to be resected, the intersegmental border, and the surgical margins could be confirmed while performing VATS segmentectomy. Complete resection was achieved in all patients. Although the pathologic margins tended to be shorter than the surgical margins on intraoperative CT images, there was a strong correlation between these 2 variables (r = 0.963, P < 0.0001). Intraoperative CT scan during VATS segmentectomy was useful for identifying the location of nonpalpable lesions, confirming anatomical intersegmental borders and securing the resection margins. Intraoperative CT navigation could enable a more definitive VATS segmentectomy for nonpalpable lesions.

Intraoperative computed tomography after tumor marking with metal clips for non-palpable lung tumors.

BACKGROUND: Locating small, non-palpable lung tumors during video-assisted thoracoscopic surgery (VATS) is difficult. In this paper, we report a simple method to identify such tumors during VATS, using intraoperative computed tomography (IO-CT). METHODS: From 2015 to 2017, we performed IO-CT scans for patients who preoperatively seemed to have non-palpable lung tumors. We initially tried to locate these tumors by finger palpation through the thoracoscopic ports. IO-CT scans were performed after marking tumors with metal clips. However, difficult-to-palpate tumors were marked by initially locating the intercostal muscle from preoperative CT. Metal clips were applied just under the intercostal muscle, and IO-CT scans were performed. After locating the tumor in relationship to the marking clips, patients would undergo wedge resections during VATS, using surgical staplers. RESULTS: We used this procedure on 21 tumors in 18 patients, including 9 non-palpable tumors and 12 palpable tumors (mean tumor size: 7.3 mm; mean distance from pleura: 6.8 mm). All tumors were identified intraoperatively, and all patients successfully underwent wedge resections during VATS, with no intra-postoperative complications. CONCLUSION: IO-CT scans after tumor marking with metal clips during VATS can accurately locate non-palpable small sized lung tumors. IO-CT scans should be indicated for tumors that are preoperatively considered to be non-palpable.

Intra-thoracic fibrous tissue induction by polylactic acid and epsilon-caprolactone copolymer cubes, with or without slow release of basic fibroblast growth factor.

OBJECTIVE: We investigated whether implantation of polylactic acid and epsilon-caprolactone copolymer (PLAC) cubes with or without basic fibroblast growth factor (b-FGF) released slowly from gelatin microspheres was able to induce fibrous tissue in the dead space remaining after pneumonectomy in the thoracic cavity. METHODS: Left pneumonectomy was performed in Japanese white rabbits. In the control group (n=6), the left thoracic cavity was closed without any treatment. In the FGF group (n=6), gelatin microspheres that released 100 microg of b-FGF were implanted into the left thoracic cavity. In the PLAC group (n=6), PLAC cubes were implanted into the left thoracic cavity. In the PLAC/FGF group (n=6), both PLAC cubes and gelatin microspheres releasing 100 microg of b-FGF were implanted into the left thoracic cavity. RESULTS: In the control and FGF groups, herniation of the heart, mediastinal shift, and overinflation of the right lung were observed. No granular tissue formation was observed. In the PLAC and PLAC/FGF groups, a dense area of newly formed soft tissue was observed, and only a mild mediastinal shift was observed during the 3-month follow-up period. Pathological examination revealed induction of fibrous and granular tissue in the left thoracic cavity. The foreign-body reaction induced by PLAC was very mild. CONCLUSIONS: Implantation of PLAC cubes with or without gelatin microspheres releasing 100 microg of b-FGF is able to induce fibrous tissue in the post-pneumonectomy dead space.