Spontaneous Bilateral Pneumothorax in a Patient with Anorexia Nervosa: The Management of Prolonged Postoperative Air Leakage.

A 24-year-old Japanese female with anorexia nervosa presented to our hospital for bilateral pneumothorax, and 12-Fr thoracostomy catheters were inserted into the bilateral pleural cavities. On hospital day 9, a thoracoscopic bullectomy was performed. However, air leakage relapsed on both sides on postoperative day 1. The air leakage on the right side was particularly persistent, and we switched the drainage to a Heimlich valve. Both lungs expanded gradually and the chest tube was removed on postoperative day 19. Passive pleural drainage might be an option for prolonged air leakage after a bullectomy in patients with anorexia nervosa.

EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery.

BACKGROUND: Primary lung tumors are sometimes resected when either pleural dissemination (PD) or malignant pleural effusion (MPE) exists. This study clarified the prognostic factors for non-small cell lung cancer (NSCLC) with either PD and MPE, or both, detected during or after surgery. PATIENTS AND METHODS: We examined patients with NSCLC from a multicenter database who had either PD, MPE, or both, detected during or after surgery between 2005 and 2015. Hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model adjusted for potential confounding factors. RESULTS: Among 9463 registered patients, PD, MPE, or both, were found in 114 patients with NSCLC during or after surgery. Primary tumor resection and exploratory thoracotomy were performed in 65 and 49 patients, respectively. In univariate analysis, adenocarcinoma, clinically undetected lymph node metastasis (c-N0 or unknown), EGFR mutation, and combination of chemotherapy or tyrosine kinase inhibitors after surgery were better prognostic factors for overall survival (OS), whereas in the multivariate analysis, adenocarcinoma, clinically undetected lymph node metastasis, and EGFR mutation were favorable independent prognostic factors in OS. Additionally, limited to patients with EGFR mutation, patients with primary lung tumor resection showed a significantly better 5-year OS than those with exploratory thoracotomy (86.4 vs. 44.8%; p < 0.001). CONCLUSION: Our findings show that surgical resection of primary tumors could improve the prognosis of patients with PD, MPE, or both, detected during or after surgery when the tumors harbor an EGFR mutation.

Randomized phase II study of daily and alternate-day administration of S-1 for adjuvant chemotherapy in completely-resected stage I non-small cell lung cancer: results of the Setouchi Lung Cancer Group Study 1301.

BACKGROUND: The aim of this multicenter, randomized phase II study was to analyze the feasibility and safety of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in patients with completely resected pathological stage I (tumor diameter > 2 cm) non-small cell lung cancer (NSCLC). METHODS: Patients were randomly assigned to receive adjuvant chemotherapy for 1 year comprising either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Group A) or a 2-week oral administration of S-1 (80 mg/m2/day) followed by 1 week of rest (Group B). The primary endpoint was feasibility, which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. RESULTS: Ninety-three patients were enrolled of whom 90 patients received S-1 treatment. Median follow-up was 66.9 months. The treatment completion rate based on an RDI of 70% or more for 6 months was 84.4% (95%CI; 70.5-93.5%) in group A and 64.4% (95%CI; 48.8-78.1%) in group B. There were no grade 4 adverse events in either group. Moderate or severe adverse events (grade 2 or grade 3) were significantly more frequent in group B (67%) compared with group A (29%, P = 0.001). The 5-year relapse-free survival rate was 87.0 and 80.9% for group A and B, respectively (P = 0.451). The 5-year overall survival rate for all patients (n = 93) was 100 and 89.4% for group A and B, respectively (P = 0.136). CONCLUSION: Alternate-day oral administration of S-1 for 1 year as adjuvant chemotherapy was demonstrated to be feasible with low toxicity in completely resected stage I (tumor diameter > 2 cm) NSCLC. TRIAL REGISTRATION: Trial registration number: UMIN000011994 . Date of registration: 10/8/2013.

[Outcome of Repeated Surgical Resections of Hepatic and Pulmonary Metastases from Colorectal Cancer].

Previous reports have demonstrated that repeated surgical resections of resectable hepatic and pulmonary metastases from colorectal cancer contribute to a better prognosis. We retrospectively assessed the outcomes of 19 patients with colorectal cancer who underwent repeated resections of hepatic and pulmonary metastases between February 2007 and February 2017. The median observation period was 69.9 months, and 26 liver and 27 lung resections were performed. The cumulative 5-year survival rates after resection of the last metastasis was 75.1% and the median disease-free survival after resection of the last metastasis was 34.7 months. Although 7 patients showed recurrence and 4 patients died, 7 patients exhibited long-term survival. Univariate analysis revealed that simultaneous liver and lung metastases were significantly predictor of poor prognosis(p=0.039). Progress of the patients in the present study were comparable to those in previous reports. Therefore, we propose that repeated surgical resection of hepatic and pulmonary metastasis from colorectal cancer could improve patient prognosis. Further studies should examine to identify more accurate prognostic factor with large series.

[Outcome of Pulmonary Metastasectomy for Hepatocellular Carcinoma].

Pulmonary metastasis of hepatocellular carcinoma (HCC) is considered a poor prognostic feature of the disease, and the utility of pulmonary resection is unclear. We evaluated clinical outcomes following pulmonary resection in 7 patients. All patients underwent video-assisted thoracic surgery (VATS). The median disease-free interval (DFI) was 14 (6-23) months. During pulmonary resection in 1 of the patients, intrahepatic recurrence was discovered and, 18 months later, this patient died of the recurrence. Of the remaining 6 patients, 2 patients developed intrahepatic recurrence and brain metastasis and died at 66 months and 10 months after pulmonary resection. Three patients are still alive and disease-free to date with a median follow-up duration of 42 (18-55) months. Of these 3 surviving patients, 2 patients had solitary pulmonary metastases and 1 patient had multiple bilateral pulmonary metastases; these patients underwent VATS once. The 7th patient underwent VATS 3 times for pulmonary metastasis and had no evidence of intrahepatic or extrahepatic recurrence. This patient died of an unrelated cause 15 months after the last pulmonary resection (47 months after the primary pulmonary resection). This study indicates that surgical resection of metachronous pulmonary metastases is associated with a favorable outcome in selected patients.

In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus.

Currently available methods for detection of tumors in vivo such as computed tomography and magnetic resonance imaging are not specific for tumors. Here we describe a new approach for visualizing tumors whose fluorescence can be detected using telomerase-specific replication-competent adenovirus expressing green fluorescent protein (GFP) (OBP-401). OBP-401 contains the replication cassette, in which the human telomerase reverse transcriptase (hTERT) promoter drives expression of E1 genes, and the GFP gene for monitoring viral replication. When OBP-401 was intratumorally injected into HT29 tumors orthotopically implanted into the rectum in BALB/c nu/nu mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. Our results indicate that OBP-401 causes viral spread into the regional lymphatic area and selectively replicates in neoplastic lesions, resulting in GFP expression in metastatic lymph nodes. This technology is adaptable to detect lymph node metastasis in vivo as a preclinical model of surgical navigation.

Revaluation of a selected segmental insufflation technique in total thoracoscopic lung segmentectomy.

We report selected insufflation technique using direct bronchial insufflation to visualize the intersegmental plane during total thoracoscopic segmentectomy. Following the transection of the bronchus using a stapler, a small incision was created in the dissected target bronchus, and direct air insufflation was performed at the small incision site. The target segment was inflated, while the preserved segments appeared to collapse, and a demarcating line was visualized between the inflated and deflated lung parenchyma. This technique quickly identifies the anatomic intersegmental plane without warranting special equipment such as jet ventilation or indocyanine green (ICG). Furthermore, this method saves time in creating inflation-deflation lines.

Surgical outcome of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy.

OBJECTIVES: Ipsilateral reoperation after pulmonary lobectomy is often challenging because of adhesions from the previous operation. We retrospectively examined the surgical outcome and prognosis of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy using a multicentre database. METHODS: We evaluated the perioperative outcomes and overall survival of 51 patients who underwent pulmonary lobectomy followed by ipsilateral anatomical resection for lung cancer between January 2012 and December 2018. In addition, patients with stage I non-small-cell lung cancer (NSCLC) were compared with 3411 patients with stage I lung cancer who underwent pulmonary resection without a prior ipsilateral lobectomy. RESULTS: Ipsilateral anatomical resections included 10 completion pneumonectomies, 19 pulmonary lobectomies and 22 pulmonary segmentectomies. Operative time was 312.2 ± 134.5 min, and intraoperative bleeding was 522.2 ± 797.5 ml. Intraoperative and postoperative complications occurred in 9 and 15 patients, respectively. However, the 5-year overall survival rate after anatomical resection followed by ipsilateral lobectomy was 83.5%. Furthermore, in patients with c-stage I NSCLC, anatomical resection followed by ipsilateral lobectomy was not associated with worse survival than anatomical resection without prior ipsilateral lobectomy. CONCLUSIONS: Anatomical resection following ipsilateral lobectomy is associated with a high frequency of intraoperative and postoperative complications. However, the 5-year overall survival in patients with c-stage I NSCLC who underwent ipsilateral anatomical resection after pulmonary lobectomy is comparable to that in patients who underwent anatomical resection without prior pulmonary lobectomy.

Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201.

BACKGROUND: It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. METHODS: Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. RESULTS: We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). CONCLUSION: Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. TRIAL REGISTRATION: Unique ID issued by UMIN: UMIN000007819 (Date of registration: Apr 25, 2012) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009128. Trial ID issued by jRCT: jRCTs061180089 (Date of registration: Mar 22, 2019, for a shift toward a "specified clinical trial" based on Clinical Trials Act in Japan) https://jrct.niph.go.jp/en-latest-detail/jRCTs061180089.

A case of multiple lung carcinoid tumors localized in the right lower lobe.

Typical pulmonary carcinoid (TC) tumors are low-grade neuroendocrine tumors and usually detected as indolent solitary tumors. We herein report a case of multiple pulmonary carcinoid tumors and tumorlets localized in the right lower lobe with no underlying lung disorders suggesting diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). A 28-year-old man with multiple 1-to-8-mm pulmonary nodules in the peripheral pulmonary parenchyma of the right lower lobe was referred to our hospital. The patient underwent a surgical biopsy. Pathological examination revealed multiple nodules composed of spindle cells, and immunohistochemistry revealed staining for chromogranin A, synaptophysin, and CD56, suggesting neuroendocrine tumors. He was diagnosed as having multiple TC tumors and tumorlets. Neuroendocrine cell hyperplasia (NECH) was also observed on some bronchioles. A follow-up CT scan after 6 months showed no changes in the sizes of the nodules and no new lesions. The present case was histopathologically compatible with DIPNECH but it occurs mainly in elderly women. The patient might be in an early stage of DIPNECH before progression to symptomatic DIPNECH. In conclusion, clinicians should consider the possibility of carcinoid tumors and tumorlets in cases with multiple pulmonary nodules even if they are localized in one lobe.

Clinical Features of Patients With Second Primary Lung Cancer After Head and Neck Cancer.

BACKGROUND: In survivors of head and neck cancer (HNC), second primary lung cancer (SPLC) often develop as a result of a common risk factor, that is, smoking. A multicenter experience was reviewed to evaluate how the history of a diagnosis of HNC affects the outcomes of patients undergoing pulmonary resection for SPLC. METHODS: A multicenter retrospective analysis of patients hospitalized between January 2012 and December 2018 was performed. From a cohort of 4521 patients undergoing therapeutic pulmonary resection for primary non-small cell lung cancer, 100 patients with a previous history of HNC (HNC group) were identified. These patients were compared with a control group consisting of 200 patients without an HNC history from the same cohort pair-matched with operating facility, age, sex, and pathologic stage of lung cancer. RESULTS: At the time of surgery for SPLC, the HNC group showed malnutrition with a lower prognostic nutritional index compared with the control group (P < .001). The HNC group was determined to have postoperative complications more frequently (P = .02). The 5-year overall survival rates in the HNC and control groups were 59.0% and 83.2%, respectively (P < .001). Statistically, HNC history, lower prognostic nutritional index, squamous cell lung cancer, and TNM stage were identified to be independently associated with poor survival. CONCLUSIONS: Patients with SPLC after primary HNC often present with malnutrition and are predisposed to postoperative complications and poor survival after pulmonary resection.

[Left lung cancer accompanied with a persistent left superior vena cava; report of a case].

A 77-year-old woman who had been treated for tongue cancer, esophageal cancer and laryngeal cancer, 25 years, 8 years and 8 months before respectively, was referred to our department because of the pulmonary tumor. Enhanced computed tomography showed a nodule of 32 mm in diameter in the left upper lobe and persistent left superior vena cava (PL-SVC). She underwent left upper lobectomy with mediastinal lymph node dissection, preserving PL-SVC. PL-SVC is a rare anomaly and may disturb the mediastinal lymph node dissection. Care should always be taken for the possibility of anomalous venous connection in performing thoracic surgery.

[Lung cancer associated with pulmonary aspergillosis in the nodule of old mycobacterial infection].

A 66-year-old man was admitted to our hospital to examine abnormal shadow in the right lung in May 2009. Chest computed tomography (CT) showed a nodule in the apex of right lung adjacent to the old shadow which was thought to be inflammatory and had been followed up since November 2002. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed significant accumulation of the isotope in the new nodule. Lung cancer was strongly suspected and the nodule with the joining lesion was surgically removed. Pathological examination revealed poorly to well differentiated papillary adenocarcinoma in the cancer lesion and aspergillosis in the necrotic and old fibrocaseous lesion. In the present case, lung cancer is thought to develop adjacent to the pulmonary aspergillosis.

[Leiomyoma of the trachea; report of a case].

Leiomyoma of the trachea is a rare benign tumor. The patient was a 44-year-old male with a chief complaint of cough. Chest X-ray and computed tomography (CT) scan demonstrated a tracheal tumor. Bronchofiberscopy revealed a polypoid round tumor in the trachea. The tumor originated from the membranous portion of the trachea without narrow stalk. Tracheal circumferential resection with primary end-to-end anastomosis was performed via right postero-lateral thoracotomy, and postoperative course was uneventful. Definitive diagnosis of tracheal leiomyoma was made by histological examination. Although the reports of transbronchial endoscopic treatment for tracheal leiomyoma were increasing, tracheal resection was selected for this case considering the risk of perforation of the membranous portion of the trachea.

Correlation of frontal prism structures and slope failures near the trench axis with shallow megathrust slip at the Japan Trench.

Since the giant 2011 Tohoku earthquake and tsunami, much research has focused on the distribution of coseismic slip at shallow depths during this subduction megathrust event. Here we present seismic images obtained in the immediate vicinity of the trench axis, that show thrust faults and fold-and-thrust type deformation structures near the epicenter of the 2011 Tohoku earthquake where the large coseismic slip has been inferred, and chaotic structure and the absence of thrust faults in northern and southern source areas. Seismic profiles show evidence of slope failures of the trench inner wall in a proposed tsunami source region around 39°-40° N, where the slips estimated from previous studies are in disagreement. Our results show that structural characteristics in the trench axis may be related to the occurrence of shallow megathrust slip and tsunamigenesis in the Japan Trench.

Endovascular treatment of ureteroarterial fistula using a covered stent, evaluated by intravascular ultrasound: a case report.

BACKGROUND: Ureteroarterial fistula is a rare life-threatening complication of indwelling ureteral stents. The mechanism has not yet been fully evaluated using intravascular imaging. CASE PRESENTATION: An-84-year-old female was referred to our unit because of large volume pulsatile bleeding from the left ureter during routine stent exchange in the urology department. The hematuria was initially managed by rapidly exchanging for a new stent; however, the patient went into hypovolemic shock due to acute blood loss. The patient underwent implantation of the bilateral ureteral stents due to urinary retention caused by retroperitoneal fibrosis 2 years ago. To prevent ureteral infection, occlusion of the stents and stone formation, the stents were exchanged every 6 months. Computed tomography revealed contact between the left ureter and the common iliac artery. Therefore, ureteroarterial fistula was suspected and endovascular therapy was performed. Although angiography did not show definite blood flow into the ureter, a soft guidewire was advanced from the subintima of the external iliac artery to the left ureter. The diagnosis of ureteroarterial fistula was confirmed. Intravascular ultrasound identified the stent in the ureter and its connection to the subintima of the external iliac artery. The ureter did not contact directly to the inner lumen of the iliac arteries according to the ultrasound findings; therefore, we considered that the risk of stent-graft infection might not be high. After coil embolization of the ipsilateral internal iliac artery, a covered stent was implanted in the external iliac artery to seal the subintimal entry. The patient had no further episodes of any gross hematuria on dual anti-platelet therapy, when the ureteral stent was exchanged three time during 1 year after the endovascular therapy. CONCLUSIONS: We demonstrated a case of ureteroarterial fistula, in which intravascular ultrasound allowed to visualize the communication between the ureter and the subintimal lumen in the external iliac artery.

Combination of oncolytic adenovirotherapy and Bax gene therapy in human cancer xenografted models. Potential merits and hurdles for combination therapy.

Cancer gene therapy and oncolytic virotherapy have been studied extensively. However, their clinical application is hampered by their weak anticancer activity. We previously constructed a replicating adenovirus (OBP-301, Telomelysin), in which the human telomerase reverse transcriptase (hTERT) promoter drives expression of the adenoviral E1 genes, and causes selective lysis of human cancer cells. We hypothesized that combination adenoviral therapy containing OBP-301 and a nonreplicating adenovirus expressing the proapoptotic Bax gene could overcome the weakness and augment the anticancer efficacy of each modality. Combination treatment resulted in marked Bax protein expression and enhanced efficacy in in vitro cell viability assay, when compared with either single treatment. However, combination treatment was not as effective in suppressing both subcutaneous and pleural disseminated tumors compared with OBP-301 treatment alone. Further investigation revealed that combination treatment resulted in suppressed E1A protein expression associated with reduced viral replication. Our results suggest that Bax gene therapy in combination with oncolytic adenovirotherapy potentially augments their antitumor activity, but further improvements may be required to maximize the combinatorial effect in vivo, for the Bax gene expression to avoid interference with production of the oncolytic virus.

Large fault slip peaking at trench in the 2011 Tohoku-oki earthquake.

During the 2011 magnitude 9 Tohoku-oki earthquake, very large slip occurred on the shallowest part of the subduction megathrust. Quantitative information on the shallow slip is of critical importance to distinguishing between different rupture mechanics and understanding the generation of the ensuing devastating tsunami. However, the magnitude and distribution of the shallow slip are essentially unknown due primarily to the lack of near-trench constraints, as demonstrated by a compilation of 45 rupture models derived from a large range of data sets. To quantify the shallow slip, here we model high-resolution bathymetry differences before and after the earthquake across the trench axis. The slip is determined to be about 62 m over the most near-trench 40 km of the fault with a gentle increase towards the trench. This slip distribution indicates that dramatic net weakening or strengthening of the shallow fault did not occur during the Tohoku-oki earthquake.