[Retrograde S(9+)10 Segmentectomy without Interlobar Fissurelectomy].

BACKGROUNDS: With increase of patients with a small-sized lung cancer, there is an increasing need for minimally invasive lung segmentectomy that can preserve respiratory function. We perform S(9+)10 segmentectomy with retrograde dissection of the pulmonary vein, bronchus, pulmonary artery, in order, without interlober fissurelectomy and staple dissection of the peripheral lung parenchyma. METHODS: Seven patients who underwent retrograde S(9+)10 segmentectomy between June, 2021 and May, 2022 in our hospital were retrospectively reviewed. RESULTS: No patient was converted to the open thoracotomy, without any complications including prolonged air leakage. The average operation time was 171 minutes( range 125 to 221), amount of bleeding was 25 ml( range 0 to 75). Median duration of chest tube insertion was 4 days( range 3 to 6), length of stay after surgery was 6 days (range 5 to 9). Pathologic stage showed pT1mi in 3 patients, pT1a in 3 patients, pT2a in 1 patient. No local recurrence was seen at this time. CONCLUSIONS: Retrograde S(9+)10 segmentectomy is feasible and facilitates interlobar procedure at the time of repeated segmentectomy or completion lobectomy.

Laser-Trélat sign improved after the resection of a tiny ground-grass nodule: a case report.

The Laser-Trélat sign refers to eruptive seborrheic keratoses accompanied by internal malignancies, mainly abdominal advanced ones. Detailed associations remain unclear, and the skin lesions do not improve with the treatment of internal malignancies in half of the patients. Herein, we report a rare case of Laser-Trélat sign that improved after resection of a 0.6-cm pulmonary ground-glass nodule: adenocarcinoma in situ. The patient requested the resection with the hopes of improving the skin lesions, though immediate resection was not indicated oncologically. With informed consent, despite possible failure in improving cutaneous diseases, thoracoscopic partial resection of the right lower lobe was performed. Fortunately, her seborrheic keratoses substantially improved after the resection, without exacerbation. To our knowledge, this is the first report describing such a clinical course. It is essential to inform patients regarding the indication of treatment for internal malignancy and its limitation in improving eruptive seborrheic keratoses.

[The Outcome of Second Anatomical Pulmonary Resection for Ipsilateral Metachronous Lung Cancer].

INTRODUCTIONS: When the first intervention for lung cancer is anatomical resection, the ipsilateral repeat anatomical resection for metachronous second lung cancer becomes technically challenging. Herein, we report the outcomes of second anatomical pulmonary resection for ipsilateral metachronous lung cancer at our institution. SUBJECTS: Sixteen consecutive patients[ 10 men and 6 women, average age 70( range 59~81) years] were reviewed in this retrospective study. These patients underwent ipsilateral repeat anatomical resection for metachronous second lung cancer between 2009 and 2020. RESULTS: All case required right-sided lung resections. The previous interventions of patients included upper lobectomy, lower lobectomy, middle lobectomy, S2 segmentectomy, and S6 and S10a segmentectomy in 9, 4, 1, 1, and 1 case, respectively. The second surgical interventions were middle lobectomy, S6 segmentectomy, upper lobectomy, lower lobectomy, S1 segmentectomy, and S2 segmentectomy, in 6, 4, 2, 2, 1, and 1 case, respectively. Postoperative complications occurred in three patients. The median follow-up period was 53.5 months. Three patients died during the follow-up period. Of the 13 patients still alive, 6 had recurrence. The five-year overall survival rate was 80%. CONCLUSIONS: Although only a few cases were assessed, the prognosis after second anatomical pulmonary resection for ipsilateral metachronous lung cancer at our institution was satisfactory.

[Completion Pneumonectomy for the Recurrence of Lung Cancer].

INTRODUCTIONS: The morbidity and mortality after completion pneumonectomy (CP) are reportedly high. We, herein, report the outcomes of CP at our institution. SUBJECTS: Nine consecutive patients [7 men and 2 women, average age of 72 years(range 44~84 years)] who underwent CP for recurrence of lung cancer during 2012~2018 were retrospectively reviewed. RESULTS: Right-sided sleeve CP was performed in two cases and left-sided CP in seven cases. The indications for surgery were lymph node metastasis of the cancer, pulmonary metastasis, and bronchial stump recurrence in 4, 3, and 2 cases, respectively. Postoperative complications occurred in six patients. One of the patients who underwent right sleeve pneumonectomy developed bronchopleural fistula and died 68 days after the surgery. The mean follow-up period was 33 months, and four patients died during follow-up. Of the 5 patients still alive, 4 had no recurrence and 1 had recurrence in the stump of the main bronchus. The five-year overall survival rate was 78%. CONCLUSIONS: Although only few cases were assessed, the prognosis after CP at our institution was relatively good.

Can the Japanese National Clinical Database risk calculator predict long-term survival of patients who undergo palliative segmentectomy for primary lung cancer?

OBJECTIVES: Selection criteria for palliative limited surgery in patients with non-small cell lung cancer (NSCLC) can vary by institution or surgeon. We retrospectively reviewed outcomes of poor-risk patients who underwent palliative segmentectomy (PS), using the National Clinical Database Risk Calculator (RC). METHODS: We retrospectively analyzed medical records of patients with NSCLC tumors ≥ 20 mm and consolidation/tumor ratios ≥ 0.5 on computed tomography, who underwent PS from January 2009 to March 2016. Median follow-up time was 47 months (range 2-102 months). RESULTS: We enrolled 67 patients (median age: 73.0 years), of whom 54 received thoracoscopic surgery and 28 received medial lymph-node dissection. The RC's mean predictive probability rate for perioperative mortality or severe complications was 7.1%. Of the 67 patients, 24 patients (43.0%) suffered post-surgical complications, including 2 (3%) who died in hospital; 17 eventually suffered NSCLC recurrences and/or metastases, 11 eventually died from NSCLC, and 17 died from other diseases. Five-year overall survival (OS) was 59.4%. When the patients were divided into high-risk (HR) and low-risk (LR) groups based on the RC, 5-year OS was significantly less in the HR group (43.9%) than in the LR group (82.2%; P < 0.05). CONCLUSION: The RC, which was developed primarily to determine perioperative risk, can predict long-term prognosis for compromised patients who undergo PS.

Benzo(e)pyrene Inhibits Endothelium-Dependent NO-Mediated Dilation of Retinal Arterioles via Superoxide Production and Endoplasmic Reticulum Stress.

Purpose: To investigate whether benzo(e)pyrene (B(e)P), a toxicant in cigarette smoke, affects the endothelium-dependent nitric oxide (NO)-induced vasodilation of the retinal arterioles, and whether oxidative stress, distinct protein kinase signaling pathways, and endoplasmic reticulum (ER) stress are associated with the B(e)P-induced effect on the retinal arterioles. Methods: In this in vitro study, porcine retinal arterioles were isolated, cannulated, and pressurized without flow. These vessels were treated with intraluminal administration of B(e)P or B(e)P plus blockers for 180 minutes. Diametric changes to agonists were recorded by videomicroscopy. Results: Intraluminal treatment with 100 µM B(e)P for 180 minutes significantly reduced the arteriolar vasodilation caused by the endothelium-dependent NO-mediated agonists bradykinin and A23187 but not that caused by endothelium-independent NO donor sodium nitroprusside. The adverse effects of B(e)P on the vasodilatory action of bradykinin were prevented by the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) inhibitor apocynin, the c-Jun N-terminal kinase (JNK) inhibitor SP600125, the p38 mitogen-activated protein kinase inhibitor SB203580, genistein, resveratrol (RSV), and the ER stress inhibitor 4-phenylbutyrate (4-PBA). The xanthine oxidase inhibitor allopurinol did not alter the effect of B(e)P on the vasodilatory action induced by bradykinin. Conclusions: B(e)P decreases the endothelium-dependent NO-induced vasodilation in the retinal arterioles through the production of superoxide from NADPH oxidase, which is linked to JNK and p38 kinase. The results suggested that ER stress is instrumental in B(e)P-induced endothelial dysfunction and that genistein and RSV might preserve endothelial function.

Regulation of p27 by ubiquitin ligases and its pathological significance in human lung carcinomas.

Down-regulation of cyclin-dependent kinase inhibitor protein p27, due to enhanced degradation, is frequently observed in various cancers. The ubiquitin ligases that mediate this degradation have been identified as S-phase kinase-associated protein-2 (Skp2), Kip1 ubiquitylation-promoting complex (KPC), and p53-inducible protein with RING-H2 domain (Pirh2) as well. We investigated the correlation among expression of these 3 ligases and p27 status in surgical specimens of human lung carcinomas by immunohistochemical analysis. Among 93 cases, expressions of p27, Skp2, KPC, and Pirh2 were found in 89.2%, 59.1%, 59.1%, and 67.7%, respectively. Down-regulation of p27 in cancer cells was frequently observed in adenocarcinoma (AC) and squamous cell carcinoma (SCC), but not in small cell carcinoma (SmCC). Overexpression of ubiquitin ligases was variously observed among histological types: Skp2 was more frequently observed in SCC and SmCC, KPC in SCC and Pirh2 in AC, followed by SCC. Several novel findings were obtained: (i) cytoplasmic p27 was observed in 8.6%, most frequently in SCC (13.3%), and correlated with nodal metastasis (P=.0044), (ii) significant inverse correlation between nuclear p27 and Pirh2 expression was observed by statistical analysis and at the cellular level, and (iii) cytoplasmic Pirh2 and total (cytoplasmic and/or nuclear) Pirh2 were significantly correlated with the nodal status (P=.0225, 0.0314), the pathological stage (P=.0213, 0.0475) and recurrence-free survival (P=.0194, 0.0482, respectively) in AC. Altogether, our data suggests that p27 and its cognate ubiquitin ligases are specifically involved in the clinical profiles, and thus, molecular targeting of these ubiquitin ligases, in particular, Pirh2, may have therapeutic value for human lung carcinomas.

Histamine-Induced Dilation of Isolated Porcine Retinal Arterioles: Role of Endothelium-Derived Hyperpolarizing Factor.

PURPOSE: Although endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles has been well described, the role of endothelium-derived hyperpolarizing factor (EDHF) in the retinal arteriolar response remains unclear. In the current study, we examined the contribution of EDHF to the retinal arteriolar dilation to the inflammatory agent histamine and investigated the signaling mechanisms underlying this vasomotor activity. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for functional study by using video microscopic techniques. The immunohistochemical staining was performed to determine histamine receptor subtypes. RESULTS: Histamine (0.1-30 µM) produced concentration-dependent dilation of retinal arterioles in a manner sensitive to H1- and H2-receptor antagonists chlorpheniramine and famotidine, respectively. Histamine-induced vasodilation was almost abolished after endothelial removal. In the intact vessels, vasodilation to histamine was partially inhibited by the inhibitors of cyclooxygenase (indomethacin), NO synthase (NG-nitro-L-arginine methyl ester, L-NAME), or Ca2+ -activated K+ (KCa) channels (apamin plus charybdotoxin). Combination of the above inhibitors abolished histamine-induced vasodilation. Residual vasodilation in the presence of indomethacin and L-NAME was further reduced by the cytochrome P450 enzyme inhibitor sulfaphenazole but not by the gap junction inhibitor carbenoxolone or the hydrogen peroxide scavenger catalase. Immunohistochemical signals for H1- and H2-receptor expression were found only in the endothelium. CONCLUSIONS: The endothelium plays an essential role in the dilation of porcine retinal arterioles to histamine via H1- and H2-receptor activation. The EDHF derived from cytochrome P450 contributed in part to this vasodilation via KCa channel activation, in addition to the endothelial release of NO and prostanoids.

Endovascular stent graft for surgical resection of lung cancer invading aortic arch: report of a 79-year-old patient.

Combined resection of the aortic arch and lung with cardiopulmonary bypass (CPB) in patients with locally advanced lung cancer is associated with high morbidity and mortality. Aortic stenting followed by complete resection might be an alternative therapeutic strategy for patients with lung cancer. Here we report a 79-year-old man with respiratory compromise who had lung cancer invading the distal aortic arch. This case study reports that combined resection of the aortic arch with left upper segmentectomy following endovascular stenting can be safely and easily performed without CPB.

Incidental bronchial injury by soft coagulation.

Soft coagulation is a hemostat system of electrosurgical units, which automatically regulates its output voltage below 200 V, to avoid excessive output that causes carbonization of the target tissue. However, this new minimally invasive technology still has the potential risk of tissue damage during surgery. We encountered three patients with bronchial injury caused by the above system; one of whom had bronchopleural fistula. This is believed to be the first report emphasizing the adverse effects of the soft coagulation system in thoracic surgery, giving a warning to the application of this convenient device.

Vasodilatory mechanisms of unoprostone isopropyl in isolated porcine retinal arterioles.

PURPOSE: To clarify the vasodilatory mechanism of unoprostone isopropyl (UI), we examined its effects on the retinal microvascular diameter to determine the dependence on the endothelium and/or smooth muscle to reveal the signaling mechanisms involved in this vasomotor activity. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded the diametric responses to UI. RESULTS: The retinal arterioles dilated in response to UI in a dose-dependent (100 pM-10 µM) manner. The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) inhibited UI-induced vasodilation. The large-conductance Ca2+-activated K channel (BKCa channel) blocker iberiotoxin also inhibited UI-induced vasodilation. The residual vasodilation after L-NAME was eliminated with co-administration of iberiotoxin. CONCLUSIONS: UI elicits dilation of the retinal arterioles mediated by NO release and BKCa channel activation.

Surgical Outcome of Video-Assisted Thoracoscopic Surgery vs. Thoracotomy for Primary Lung Cancer >5 cm in Diameter.

OBJECTIVES: The indications for video-assisted thoracoscopic surgery (VATS) for advanced-stage lung cancer are expanding, but the criteria vary among institutions. This study compared the minimal invasiveness and oncologic validity of VATS lobectomy and thoracotomy lobectomy for the treatment of large-diameter primary lung cancer. METHODS: We retrospectively reviewed clinical features and surgical outcomes of 68 patients who underwent anatomical pulmonary resection for primary lung cancer of >5-cm diameter from July 2006 to March 2013. The patients were divided into a VATS group (Group V, n = 35) and a thoracotomy group (Group T, n = 33). RESULTS: Group V exhibited less intraoperative bleeding (p = 0.012) and had a shorter length of postoperative hospital stay (p = 0.024). The 1- and 5-year overall survival rates were 91.3% and 39.3% in Group V and 84.8% and 56.9% in Group T, respectively (p = 0.48). Multivariate analysis showed that limited lymph node dissection contributed to local recurrence. The extraction bag lavage cytology in Group V revealed that the positivity rate was 35.7%. CONCLUSIONS: VATS for primary lung cancer of >5-cm diameter is similar to thoracotomy in terms of surgical outcomes. Large tumors must be carefully maneuvered during VATS to prevent cancer cell spillage.

Beraprost sodium, a stable prostacyclin analogue, elicits dilation of isolated porcine retinal arterioles: roles of eNOS and potassium channels.

PURPOSE: Prostacyclin (PGI2) is usually described as an endoEDRFsthelium-derived relaxing factor, but the vasoreactivity to PGI2 in the retinal arterioles and the underlying mechanisms are not fully understood. We examined the effects of PGI2 on the retinal microcirculation using beraprost sodium (BPS), a stable PGI2 analogue, and the signaling mechanisms involved in this vasomotor activity. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded the diametric responses to BPS. RESULTS: Beraprost sodium elicited dose-dependent (0.1 pM-0.1 µM) vasodilation of the retinal arterioles that was abolished by the PGI2 receptor (IP) antagonist CAY10441. Beraprost sodium-induced vasodilation decreased by 50% after the endothelium was removed and was inhibited by the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) comparable with denudation. Inhibition of soluble guanylyl cyclase by 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and blockage of protein kinase A (PKA) by Rp-8-Br-cAMPS were comparable to L-NAME. Beraprost sodium-induced vasodilation was also inhibited by the nonselective potassium channel inhibitor, tetraethylammonium, and the adenosine triphosphate-sensitive potassium (KATP) channel blocker, glibenclamide. Residual vasodilation in the presence of glibenclamide decreased further with subsequent application of ODQ. CONCLUSIONS: Beraprost sodium, a stable PGI2 analogue, causes vasodilation of the retinal arterioles mediated via the IP receptor. The current findings suggest that BPS elicits endothelium-dependent and -independent dilation of the retinal arterioles mediated by NO induced by activation of PKA in the endothelium and the KATP channel activation in the vascular smooth muscle, respectively.

Extraction bag lavage cytology during video-assisted thoracoscopic surgery for primary lung cancer.

OBJECTIVES: Sample extraction from the thoracic cavity through an intercostal space during video-assisted thoracoscopic surgery can result in cancer cell contamination by tumour crushing and tumour cell extravasation, and may have adverse effects on the surgical outcome. Lavage cytology of the sample extraction bag was investigated to clarify the risk of cancer cell spillage and identify the clinicopathological features associated with susceptibility to cancer cell spillage during extraction. METHODS: Lavage cytology of the sample extraction bag was investigated in 464 patients with negative pleural lavage cytology who underwent lung resection for primary lung cancer via video-assisted thoracoscopic surgery between January 2010 and December 2012. The surgical procedures, pathological findings and clinical course were evaluated by hospital record review. RESULTS: The incidence of positive bag lavage cytology (BLC) was 13.6%. Statistically significant factors associated with susceptibility to BLC positivity were tumour size, standardized uptake value of positron emission tomography, pathological features such as pathological N score, pleural invasion, vascular invasion and papillary-predominant adenocarcinoma. Among patients with Stage I lung cancer, the survival rate was significantly lower in the BLC-positive group than in the BLC-negative group. CONCLUSIONS: BLC positivity can be related to oncological characteristics such as tumour invasiveness and adhesiveness as opposed to tumour size and surgical margin, and may help to determine the prognosis of Stage I lung cancer. The sample extraction bag must be carefully manoeuvred through the intercostal space to prevent cancer cell dissemination to the chest wall or thoracic cavity.

Surgical outcomes after superior vena cava reconstruction with expanded polytetrafluoroethylene grafts.

OBJECTIVES: Graft occlusion is a problem after superior vena cava (SVC) reconstruction for thoracic malignancy. Expanded polytetrafluoroethylene (ePTFE) is considered to be an optimal material for venous reconstruction. METHODS: We reviewed the hospital records of 13 patients who underwent complete resection of thoracic malignancy invading the SVC, including SVC reconstruction with ePTFE grafts. Single bypass grafting was performed in two patients (one right-sided, one left-sided) and double bypasses grafting was performed in the other patients. All patients received antithrombotic therapy after surgery. Eight patients died of recurrence or other disease during the follow-up period (range 5-41 months). RESULTS: Of the 24 grafts in 13 patients, graft patency was confirmed in 20 grafts in 9 patients at a mean time follow-up time of 47.8 ± 50.0 months after surgery. In the remaining four grafts in four patients, occlusion was diagnosed at a mean time of 1.25 ± 0.50 months after surgery. All obstructed grafts were left-sided bypass grafts in patients who underwent double bypass grafting, and did not result in SVC syndrome. CONCLUSIONS: SVC reconstruction with ringed ePTFE grafts was safe and had good outcomes. In patients who underwent double bypasses grafting, the left-sided bypass grafts were susceptible to occlusion.

[Surgical intervention for residual space empyema and bronchopleural fistula after major pulmonary resection].

Residual space empyema, that is a life threatening complication after major pulmonary resection, is based on postresectional hematoma, wound suppuration, and/or bronchopleurl fistula, demanding different strategies from parapneumonic empyema. Optimal managements should be occasionally completed in relation to the patient's physical conditions, serological findings, pathogens, and bronchopleural fistula. Bronchoscopic intervention can be a useful tool for a bronchopleural fistula when small. Thoracoscopic intervention can overcome the intractable residual space empyema. These interventions can save such invasive procedure as open window thoracotomy or thoracoplasty leading to damage pulmonary function as well as cosmetics, and prolong hospitalization. Vacuum-assisted closure system other than conventional thoracoplasty or thoracomyoplasty can be of help to obliterate the residual space empyema cavity after open window thoracotomy.

[Stump recurrence after pulmonary metastasectomy from colorectal cancer].

Pulmonary metastasectomy with wedge resection is an ideal procedure in terms of less invasiveness and preservation of respiratory function, while local recurrence is a major problem. The goal of this study was to verify risk factors of stump recurrence after pulmonary metastasectomy from colorectal cancer. Pulmonary metastasectomies including 112 operations for 131 lesions in 85 patients with colorectal cancer were performed in our department since March, 2005 until the end of 2010. In our cases, stump recurrence significantly occurred in patients who underwent wedge resection than segmentectomy or lobectomy. Stump recurrence developed in 14 operations among 62 wedge resections (recurrence rate: 23%). Diameter more than 10 mm and distance between pleura and deepest end of the tumor (depth value) more than 14 mm were risk factors as stump recurrence. Tumor diameter and depth value can be a decisional factor for wedge resection in pulmonary metastasectomy in the colorectal cancer patients.

[Clinicopathological study of small lung cancer (diameter of 2 cm or less) by uptake value of 18F-fluorodeoxyglucose].

18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for lung cancer may be a biomarker for malignancy as well as a useful tool for detection of nodal involvement and distant metastasis. The goal of this study was to clarify a relationship between clinicopathological findings and maximum standardized uptake value( SUVmax) obtained by preoperative PET in patients with non-small cell lung cancer in diameter of 2 cm or less. Between January 2008 and April 2011, 124 patients( 54 men and 70 women) with non-small cell lung cancer in diameter of 2 cm or less undergoing lobectomy or segmentectomy were enrolled. The relationship between SUVmax and clinicopathological findings as tumor diameter, histological type, pleural invasion, vascular invasion, lymphatic permeation and nodal involvement were analyzed. Correlation between SUVmax and findings such as vascular invasion and lymphatic permeation showed relatively strong in the patients with adenocarcinoma, on the contrary to the correlation in the patients with non-adenocarcinoma. No tumor showing SUVmax of 2 or less showed vascular invasion and/or lymphatic permeation as well as nodal involvement in any patients with adenocarcinoma. SUVmax of the primary tumor in diameter of 2 cm or less, can be a useful biomarker which indicates a surgical candidate for sublobar pulmonary resection as well as mediastinal nodal dissection, especially in patients with adenocarcinoma.

[Clinical outcome after video-assisted thoracic surgery (VATS) for clinical stage I lung cancer with pathologically nodal involvement].

The lymph node dissection with video-assisted thoracic surgery( VATS) was technically feasible and the remnant lymph nodes and tissues were 2% to 3%, which seems acceptable for clinical stage I lung cancer. Surgical outcome after VATS for clinical stage I lung cancer with pathologically nodal involvement, however, remains unclear. Medical records of 72 patients who had clinical stage I non small cell lung cancer with pathologically nodal involvement( pN1:21 patients, pN2:51 patients) and underwent VATS lobectomy or segmentectomy with mediastinal dissection between January 2005 and December 2010, were retrospectively reviewed. Postoperative recurrence and survival were studied. Remnant nodal recurrence occurred in 8 patients with pN1 (recurrence rate 38%) and 15 patients with pN2 (recurrence rate 29%). The 1- and 3-year disease free survival rate was 87% and 68%. The 1- and 3-year survival rate was 100% and 79%. This study suggested that VATS is acceptable for patients with clinical stage I lung in terms of survival rate, cancer with pN1. In a view point of remnant nodal recurrence, a more skillful dissection procedure is required.

Muscle plombage for extensive bronchial necrosis after right lower lobectomy.

Bronchial stump necrosis is a lethal complication after pulmonary resection. We report a patient who had extensive necrosis of the intermediate bronchus after right lower lobectomy. The large bronchial defect was successfully fixed with latissimus dorsi muscle and replaced by bronchial epithelialization.