A novel dual-covering method in video-assisted thoracic surgery for pediatric primary spontaneous pneumothorax.

BACKGROUND: Primary spontaneous pneumothorax (PSP) generally occurs in young adults, whereas pediatric PSP is uncommon. It is difficult to source reliable data on pediatric PSP, the management of which is based on guidelines for adult PSP; however, the rate of recurrence after video-assisted thoracoscopic surgery (VATS) for pediatric PSP is reported to be higher. METHODS: We reviewed retrospectively a collective total of 66 surgical cases of a first pneumothorax episode in 46 children under 16 years of age, who were treated at our hospital between February, 2005 and November, 2017. RESULTS: The surgical cases were divided into two groups, depending on how the treated lesions were covered. In the dual-covering (DC) group, the PSP was covered by oxidized regenerated cellulose and polyglycolic acid (8 patients; 13 cases) and in the single-covering (SC) group, the PSP was covered by oxidized regenerated cellulose (38 patients; 53 cases). There was no incidence of recurrence after surgery in the DC group, but 17 cases (32.1%) of recurrence after surgery in the SC group. This difference was significant. CONCLUSION: The DC method prevented the recurrence of PSP more effectively than the SC method after VATS in pediatric patients. Long-term follow-up after VATS for pediatric PSP is also important because of the risk of delayed recurrence.

[A SURGICAL CASE OF MYCOBACTERIUM KANSASII LUNG DISEASE MIMICKING PRIMARY LUNG CANCER].

We report a rare surgical case of a solitary pulmonary nodule due to Mycobacterium kansasii. A 59-year-old man was admitted to our hospital for examination of an abnormal shadow in the left upper lobe incidentally found on a chest radiogram. Computed tomography of the chest showed that the nodule was located in the left segment 1+2 and was irregularly shaped with a diameter of 35 mm. Thoracic fluorine-18 fluoro-deoxy-glucose positron emission tomography showed a high metabolic pulmonary lesion, with a maximum standardized uptake value of 5.1, consistent with findings for lung cancer. A bronchoscopy was performed to establish the diagnosis of lung cancer; however, it failed to show malignant cells. Because we could not confirm the diagnosis by bronchoscopic examination, video-assisted thoracoscopic surgery was performed. The intraoperative rapid diagnosis of the nodule was epithelioid cell granuloma. Smear test of the resected specimen was positive for acid-fast bacilli, and a culture was also positive for mycobacteria, which were identified as Mycobacterium kansasii. Antibiotic treatment for M. kansasii infection was administered for a year after the surgical resection. Few cases of Mycobacterium kansasii infection present with solitary pulmonary nodules.

[Bronchial hamartoma in subsegmental bronchus; report of a case].

We report a rare surgical case of a bronchial hamartoma in subsegmental bronchus. A 70-year-old man was incidentally pointed out an abnormal chest shadow without any complaints. Chest computed tomography revealed a round nodule with diameter of 15 mm in the right upper lobe. The bronchoscopic examination revealed complete obstruction of right B2a by the tumor. Right S2 segmentectomy was done to make a definite diagnosis and to prevent possible obstructive pneumonia. Histopathological examination revealed that the tumor was a benign cartilage bronchial hamartoma.

[Synchronous multiple primary lung and colon cancers].

We report a rare surgical case of synchronous multiple primary lung cancers with synchronous multiple colon cancers. A 74-year-old woman was incidentally pointed out abnormal chest shadows. Chest computed tomography revealed 2 nodules in the right upper and middle lobe. Transbronchilal lung biopsy (TBLB) was done, and the tumor in the middle lobe was diagnosed as adenocarcinoma. In addition, positron emission tomography pointed out colon cancer. Colon fiber revealed multiple colon polyps and colon cancers. Immunostaining with thyroid transcription factor (TTF)-1 and Napsin-A for TBLB specimen was done to distinguish their association. With the diagnosis as primary lung cancer, we performed right upper and middle lobectomy with lymph node dissection. These tumors were pathologically diagnosed as synchronous multiple primary lung cancers with adenocarcinoma and squamous cell carcinoma. Several months later, colon regions were resected through colonoscopic endometric mucosal resection and left hemicolectomy.

MicroRNA down-regulated in human cholangiocarcinoma control cell cycle through multiple targets involved in the G1/S checkpoint.

UNLABELLED: MicroRNAs (miRs) recently emerged as prominent regulators of cancer processes. In the current study we aimed at elucidating regulatory pathways and mechanisms through which miR-494, one of the miR species found to be down-regulated in cholangiocarcinoma (CCA), participates in cancer homeostasis. miR-494 was identified as down-regulated in CCA based on miR arrays. Its expression was verified with quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). To enforce miR expression, we employed both transfection methods, as well as a retroviral construct to stably overexpress miR-494. Up-regulation of miR-494 in cancer cells decreased growth, consistent with a functional role. mRNA arrays of cells treated with miR-494, followed by pathway analysis, suggested that miR-494 impacts cell cycle regulation. Cell cycle analyses demonstrated that miR-494 induces a significant G1/S checkpoint reinforcement. Further analyses demonstrated that miR-494 down-regulates multiple molecules involved in this transition checkpoint. Luciferase reporter assays demonstrated a direct interaction between miR-494 and the 3'-untranslated region of cyclin-dependent kinase 6 (CDK6). Last, xenograft experiments demonstrated that miR-494 induces a significant cancer growth retardation in vivo. CONCLUSION: Our findings demonstrate that miR-494 is down-regulated in CCA and that its up-regulation induces cancer cell growth retardation through multiple targets involved in the G1-S transition. These findings support the paradigm that miRs are salient cellular signaling pathway modulators, and thus represent attractive therapeutic targets. miR-494 emerges as an important regulator of CCA growth and its further study may lead to the development of novel therapeutics.

COVID-19 pneumonia and an indelible ground-glass nodule.

When a chest computed tomography (CT) scan is performed in the diagnosis and treatment of coronavirus disease 2019 (COVID-19) pneumonia, the possibility of lung neoplasm should be kept in mind if the ground-glass nodule (GGN) shows features that are non-specific for viral infection, such as solitary nature, relative roundness, well-defined borders, and distance from the pleura.

Pleurography (thoracography) for pleural fistulas: A case series.

BACKGROUND: Pleurography (PG) has been described previously but has not gained popularity. PG can determine the exact air leak points in the lung, which is important for treating pneumothorax and pleural fistulas. We believe that the usefulness of PG should be reassessed, and here we describe the method, air leak detection rate, and common complications. METHODS: From the 1210 cases of pleural fistulas that were treated at our institution between March 2015 and October 2018, 275 patients with recurrent primary pneumothorax or secondary spontaneous pneumothorax were selected for this study. PG was performed in 127 patients with persistent air leakage during exhalation. In addition, 35 patients with postoperative complications of air leakage persisting for 7 days or longer were included. RESULTS: Air leak points were detected in 119 patients (73%), in the apex of the lung in 65 cases, in the basal segment in 13 cases, and in the middle lobe or lingular segment in 9 cases. There were 8 cases of hilar lesions, 12 cases of S6 lesions, 8 cases of upper lobe lesions other than apex, and 4 cases of upper mediastinal lesions. Complications within 30 days were observed in 10 cases (6.2%), with 8 grade 2 cases involving fever, 1 grade 3 case involving infection, and one grade 1 case with abdominal distension. CONCLUSIONS: The incidence of grade ≥3 adverse events after PG was 0.6%, which is considered acceptable. Our findings suggest that PG is a safe examination method to identify air leaks before surgery for pleural fistulas.

An intrathoracic giant tumour and vanishing lung cyst after tumour resection.

A 65-year-old woman was brought to the emergency unit with an approximately 6-month history of persistent fever and cough. Chest computed tomography (CT) demonstrated a 16-cm heterogeneous mass with adjacent large cyst (approximately 4.0 cm). The patient underwent CT-guided biopsy, and benign solitary fibrous tumour (SFT) was immunohistochemically diagnosed. As the symptoms were thought to be due to enlargement of the tumour, surgery was deemed necessary, and the tumour was successfully resected. Based on morphological and immunohistochemical examination of the resected specimen, the final diagnosis was dedifferentiated SFT (DSFT). Follow-up CT verified disappearance of the pulmonary cyst. The cyst was speculated to be caused by a check valve mechanism, which may also suggest a rapid growth of the tumour. At the time of writing, 2 years post-operatively, no tumour recurrence has been identified. This represents the first report of intrathoracic giant DSFT with a cystic lesion returning to normal lung parenchyma.

Ingenuity of minimally invasive thoracoscopic lobectomy for undiagnosed pulmonary tumour.

A 51-year-old man was referred to our hospital, with a dumbbell-shaped nodule measuring 40 mm in the right upper lobe of the lung. He was a current smoker with diabetes mellitus and bronchial asthma. The transbronchial biopsy was performed. However, definitive diagnosis was not obtained from the excised specimens. Bacterial culture of bronchial lavage fluid also yielded negative results, including for tuberculosis. After eight months of observation, the tumour had slightly increased in size. Surgery was planned to resect the tumour for definitive diagnosis. Because of the size of the tumour, a lobectomy of the lung was scheduled with the patient's consent. Four small incisions, each less than 1.2 cm long, were made in the chest wall for thoracoscopic surgery. To remove the specimen, we made a 3-cm longitudinal incision 1 cm below the xiphisternal joint. The patient complained of no chest pain after surgery. The post-operative course was uneventful.

RNA interference targeting against S100A4 suppresses cell growth and motility and induces apoptosis in human pancreatic cancer cells.

S100A4 protein belongs to the S100 subfamily, which has grown to be one of the large subfamilies of the EF-hand Ca(2+)-binding proteins, and overexpression of S100A4 is suggested to associate with cell proliferation, invasion, and metastasis. We observed frequent overexpression of S100A4 in pancreatic cancer cell lines and further analyzed RNAi-mediated knockdown to address the possibility of its use as a therapeutic target for pancreatic cancer. The specific knockdown of S100A4 strongly suppressed cell growth, induced G2 arrest and eventual apoptosis, and decreased cell migration. Furthermore, microarray analyses revealed that knockdown of S100A4 induced expression of the tumor suppressor genes PRDM2 and VASH1. Our present results suggest the possibility that the inhibition of S100A4 can be utilized in antitumor applications for patients with pancreatic cancer.

Modified marionette technique for uniportal video-assisted thoracic surgery: a case report.

BACKGROUND: The current state of thoracoscopic technology allows less invasive surgical procedures and requires fewer ports and incisions. Totally video-assisted thoracic surgery with a single port has emerged as the least invasive thoracoscopic approach. However, uniportal video-assisted thoracic surgery brings about considerable difficulties, necessitating the development of skillful techniques as well as specific surgical devices. In such situations as dense pleural adhesion and anatomical abnormality, it may be more burdensome, necessitating the conversion to conventional multiportal video-assisted thoracic surgery or even to thoracotomy. To troubleshoot these situations, we herein propose the use of additional technique which could support to sustain the confident operative field for uniportal video-assisted thoracic surgery. This procedure also provides the same cosmetic outcomes as uniportal video-assisted thoracic surgery. CASE PRESENTATION: A previously healthy, 77-year-old female was referred to our hospital, with a lung adenocarcinoma measuring 28 mm in the right upper lobe. Uniportal video-assisted thoracoscopic surgery was planned to resect the tumor. During operation, we found the incomplete interlobar fissure between the upper and the middle lobe and the abnormal lobulation of the upper lobe. Therefore, the modified marionette technique was introduced to make the procedure safer and easier. This technique proposed herein consists of employing the untethered gripping forceps to retract the lung, not requiring additional traumatic trocars. The postoperative course was uneventful and the patient `was discharged in 1 week after a modified uniportal video-assisted thoracic surgery for the right upper lobectomy. CONCLUSIONS: The modified marionette technique produced sufficient operative views to attain uniportal video-assisted thoracic surgery safely in this case, rendering operative conversion unnecessary.

siRNA targeting against EGFR, a promising candidate for a novel therapeutic application to lung adenocarcinoma.

OBJECTIVE: To understand the molecular pathogenesis of lung cancer and to establish a novel therapeutic application, we examined the genetic alterations in lung cancer, and studied the effects of gefitinib and siRNA-mediated knockdown of EGFR on lung cancer. METHODS: We analyzed mutations in EGFR, KRAS, TP53, and ERBB2 in 198 surgically resected lung cancer specimens. We then analyzed the effects of gefitinib and siRNA treatment on lung adenocarcinoma cell lines. RESULTS: Mutations in EGFR were found only in adenocarcinoma (35 of 106 adenocarcinoma), mainly in females (73%). Mutually exclusive mutations of EGFR and KRAS genes were observed. Mutations of EGFR were well associated with a positive response to gefitinib. Cells with EGFR mutations were very sensitive to gefitinib as well as siRNA-mediated knockdown of EGFR, those with KRAS mutations responded poorly, and those without mutations of KRAS and EGFR showed moderate responses to both treatments. CONCLUSIONS: Our present results imply that (1) mutation analyses of EGFR and KRAS provide valuable information about whether or not to apply treatments targeting against EGFR and the selection of dosage for such treatments, and (2) siRNA-mediated knockdown is effective in lung adenocarcinomas with EGFR mutation, probably in those with resistance to gefitinib by acquired mutation in EGFR.

[A case of primary lung adenocarcinoma accompanied by Ewing's sarcoma successfully treated with ifosfamide].

We report a patient with primary lung adenocarcinoma who had Ewing's sarcoma and was successfully treated with ifosfamide. A 56-year-old Japanese man was referred to the Orthopedic Department of our hospital with a complaint of pain on his hip, ischuria, and dyschezia (vesicorectal disorder). MRI showed a mass in the sacrum. Open biopsy revealed Ewing's sarcoma (T2N0M0G4, Stage II B). Chest CT to screen showed an abnormal shadow in the left pulmonary lower lobe (S10). Bronchoscopic examination revealed primary lung adenocarcinoma(cT2N0M0, Stage I B). Because of a severe hip pain, treatment for Ewing's sarcoma by high-dose ifosfamide (day 1: 4 g/m2/day --> day 2-7: 2 g/m2/day: total 14 g/m2) was given in one course before lung surgery. The lung adenocarcinoma became small, the reduction ratio of the tumor was 26.5% and the tumor changed into a cavity. No serious adverse effect was observed.

A total pleural covering of absorbable cellulose mesh prevents pneumothorax recurrence in patients with Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is a recently recognized inherited multiple cystic lung disease causing recurrent pneumothoraces. Similarly to the lesions in patients with lymphangioleiomyomatosis (LAM), the pulmonary cysts are innumerable and widely dispersed and cannot all be removed. We recently described a total pleural covering (TPC) that covers the entire visceral pleura with oxidized regenerated cellulose (ORC) mesh. TPC successfully prevented the recurrence of pneumothorax in LAM patients. The purpose of this study was to evaluate the effect of an ORC pleural covering on pneumothorax recurrence in BHDS patients. RESULTS: This retrospective study enrolled a total of 81 pneumothorax patients with the diagnosis of BHDS who underwent 90 covering surgeries from January 2010 to August 2017 at Tamagawa Hospital. During the first half of the study period, a lower pleural covering (LPC) which covered the affected area with ORC mesh was mainly used to treat 38 pneumothoraces. During the second half of the study period, TPC was primarily performed for 52 pneumothoraces. All the thoracoscopic surgeries were successfully performed without serious complications (≥ Clavien-Dindo grade III). The median follow-up periods after LPC/TPC were 66/34 months, respectively. Pneumothorax recurrence rates after LPC at 2.5/5/7.5 years postoperatively were 5.4/12/42%, respectively; none of the patients who had underwent TPC developed postoperative pneumothorax recurrence (P = 0.032). CONCLUSIONS: TPC might be an effective option for surgical treatment of intractable pneumothorax in patients with BHDS.

Two Kinds of Cystic Lung Lesions with Pulmonary Lymphangioleiomyomatosis in a Male.

A 34-year-old male with frequent recurrence of right pneumothorax was admitted to our hospital. He was a current smoker and outwardly male without genital aplasia. He was diagnosed as tuberous sclerosis complex (TSC) at 2 year-old and underwent transcatheter arterial embolization for right renal hemorrhage due to renal tumor 2 years ago. Chest Computed Tomography showed that he had multiple tiny round cystic lesions with thin wall in both lungs. The recurrent pneumothorax was expected to be associated with TSC-Lymphangioleiomyomatosis (LAM). Video-assisted thoracic surgery was successfully performed. The operative and histological findings revealed that the bullae were classified into two groups; emphysematous bullae and bullae due to LAM. His postoperative course was uneventful. TSC-LAM is extremely rare, but in some cases the clinical recognition might be escaped due to subtle findings of bullae in early LAM, resulting in diagnosis as spontaneous pneumothorax.

Left-Sided Catamenial Pneumothorax with Thoracic Endometriosis and Bullae in the Alveolar Wall.

Catamenial pneumothorax (CP) is generally caused by intraperitoneal air leaking from the uterus into the thoracic cavity via a defect in the endometrial tissue of the diaphragm and is usually detected in the right thorax. We report a case of left-sided CP caused by endometriosis in the visceral pleura and with no abnormal findings in the diaphragm. A 33-year-old female patient presented at the end of a course of low-dose contraceptive pills for pelvic endometriosis, with spontaneous pneumothorax in the left chest. Chest CT revealed a bulla in the left upper lung lobe. The patient underwent partial resection of the lung. Immunohistochemistry confirmed the presence of endometrial stromal tissue in the visceral pleura and confirmed this as the cause of pneumothorax since there were no observable abnormalities in the diaphragm. This case suggests that immunohistochemical examination of patients with spontaneous pneumothorax can detect alternative endometrial lesions.

A Total Pleural Covering for Lymphangioleiomyomatosis Prevents Pneumothorax Recurrence.

BACKGROUND: Spontaneous pneumothorax is a major and frequently recurrent complication of lymphangioleiomyomatosis (LAM). Despite the customary use of pleurodesis to manage pnenumothorax, the recurrence rate remains high, and accompanying pleural adhesions cause serious bleeding during subsequent lung transplantation. Therefore, we have developed a technique of total pleural covering (TPC) for LAM to wrap the entire visceral pleura with sheets of oxidized regenerated cellulose (ORC) mesh, thereby reinforcing the affected visceral pleura and preventing recurrence. METHODS: Since January 2003, TPC has been applied during video-assisted thoracoscopic surgery for the treatment of LAM. The medical records of LAM patients who had TPC since that time and until August 2014 are reviewed. RESULTS: TPC was performed in 43 LAM patients (54 hemithoraces), 11 of whom required TPC bilaterally. Pneumothorax recurred in 14 hemithoraces (25.9%) from 11 patients (25.6%) after TPC. Kaplan-Meier estimates of recurrence-free hemithorax were 80.8% at 2.5 years, 71.7% at 5 years, 71.7% at 7.5 years, and 61.4% at 9 years. The recurrence-free probability was significantly better when 10 or more sheets of ORC mesh were utilized for TPC (P = 0.0018). TPC significantly reduced the frequency of pneumothorax: 0.544 ± 0.606 episode/month (mean ± SD) before TPC vs. 0.008 ± 0.019 after TPC (P<0.0001). Grade IIIa postoperative complications were found in 13 TPC surgeries (24.1%). CONCLUSIONS: TPC successfully prevented the recurrence of pneumothorax in LAM, was minimally invasive and rarely caused restrictive ventilatory impairment.

Computed tomographic images reflect the biologic behavior of small lung adenocarcinoma: they correlate with cell proliferation, microvascularization, cell adhesion, degradation of extracellular matrix, and K-ras mutation.

BACKGROUND: We previously reported that the computed tomographic M/L ratio (area of the tumor in the mediastinal computed tomographic image/area of the tumor in the lung computed tomographic image) of small peripheral lung adenocarcinoma is correlated with patient prognosis. METHODS: Immunostaining for p53, bcl-2, Ki-67, vascular endothelial growth factor, CD34, matrix metalloproteinase 2, matrix metalloproteinase 9, tissue inhibitor of matrix metalloproteinase 2, and mutation of K-ras was assessed in 131 surgically resected, primary peripheral lung adenocarcinomas of 30 mm or less in maximum diameter to clarify the relationship between computed tomographic findings and biologic activities. RESULTS: The numbers of patients with high labeling indexes of Ki-67 and high expression of vascular endothelial growth factor, CD34, matrix metalloproteinase 2, and matrix metalloproteinase 9 in the solid-type group (computed tomographic M/L ratio > or = 50%) were significantly higher than those in the faint density-type group (computed tomographic M/L ratio < 50%; P = .04 for Ki-67, P = .03 for vascular endothelial growth factor, P = .0009 for CD34, P = .001 for matrix metalloproteinase 2, and P = .00001 for matrix metalloproteinase 9). The number of patients with high levels of CD44v6 or tissue inhibitor of matrix metalloproteinase 2 staining in the faint density-type group was significantly higher than that in the solid-type group (P = .02 for CD44v6 and P = .01 for tissue inhibitor of matrix metalloproteinase 2). Independent variables capable of predicting computed tomographic M/L ratio included CD34, matrix metalloproteinase 2, matrix metalloproteinase 9, and tissue inhibitor of matrix metalloproteinase 2 (P = .0093, P = .0003, P = .0027, and P = .01, respectively; binary logistic regression analysis). CONCLUSIONS: Our results suggest that the computed tomographic image of small lung adenocarcinoma is correlated with biologic activities and thus provides possible prognostic information.

Biopsy with thermally-responsive untethered microtools.

Thermally activated, untethered microgrippers can reach narrow conduits in the body and be used to excise tissue for diagnostic analyses. As depicted in the figure, the feasibility of an in vivo biopsy of the porcine bile duct using untethered microgrippers is demonstrated.