Efficiency of eSource Direct Data Capture in Investigator-Initiated Clinical Trials in Oncology.

BACKGROUND: Clinical trials have become larger and more complex. Thus, eSource should be used to enhance efficiency. This study aimed to evaluate the impact of the multisite implementation of eSource direct data capture (DDC), which we define as eCRFs for direct data entry in this study, on efficiency by analyzing data from a single investigator-initiated clinical trial in oncology. METHODS: Operational data associated with the targeted study conducted in Japan was used to analyze time from data occurrence to data entry and data finalization, and number of visits to the site and time spent at the site by clinical research associates (CRAs). Additionally, simulations were performed on the change in hours at the clinical sites during the implementation of eSource DDC. RESULTS: No difference in time from data occurrence to data entry was observed between the DDC and the transcribed data fields. However, the DDC fields could be finalized 4 days earlier than the non-DDC fields. Additionally, although no difference was observed in the number of visits for source data verification (SDV) by CRAs, a comparison among sites that introduced eSource DDC and those that did not showed that the time spent at the site for SDV was reduced. Furthermore, the simulation results indicated that even a small amount of data to be collected or a small percentage of DDC-capable items may lead to greater efficiency when the number of subjects per site is significant. CONCLUSIONS: The implementation of eSource DDC may enhance efficiency depending on the study framework and type and number of items to be collected.

Spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support: a case report.

BACKGROUND: Intercostal artery bleeding often occurs in a single vessel; in rare cases, it can occur in numerous vessels, making it more difficult to manage. CASE PRESENTATION: A 63-year-old Japanese man was admitted to the emergency department owing to sudden chest and back pain, dizziness, and nausea. Emergency coronary angiography revealed myocardial infarction secondary to right coronary artery occlusion. After intra-aortic balloon pumping, percutaneous coronary intervention was performed in the right coronary artery. At 12 hours following percutaneous coronary intervention, the patient developed new-onset left anterior chest pain and hypotension. Contrast-enhanced computed tomography revealed 15 sites of contrast extravasation within a massive left extrapleural hematoma. Emergency angiography revealed contrast leakage in the left 6th to 11th intercostal arteries; hence, transcatheter arterial embolization was performed. At 2 days after transcatheter arterial embolization, his blood pressure subsequently decreased, and contrast-enhanced computed tomography revealed the re-enlargement of extrapleural hematoma with multiple sites of contrast extravasation. Emergency surgery was performed owing to persistent bleeding. No active arterial hemorrhage was observed intraoperatively. Bleeding was observed in various areas of the chest wall, and an oxidized cellulose membrane was applied following ablation and hemostasis. The postoperative course was uneventful. CONCLUSION: We report a case of spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support that was difficult to manage. As bleeding from numerous vessels may occur during antithrombotic therapy, even without trauma, appropriate treatments, such as transcatheter arterial embolization and surgery, should be selected in patients with such cases.

Dose Optimization of Intravenous Indocyanine Green for Malignant Lung Tumor Localization.

Background: Intravenously administered indocyanine green (ICG) accumulates in lung tumors, facilitating their detection via a fluorescence spectrum measurement. This method aids in identifying tumor locations that are invisible to the naked eye. We aim to determine the optimal ICG dose and administration method for accurate tumor identification during lung resection surgeries, utilizing a novel ICG fluorescence spectroscopy system for precise tumor localization. Materials and Methods: ICG should be dissolved in the provided solution or distilled water and administered intravenously approximately 24 h before surgery, beginning with an initial dose of 0.5 mg/kg. If the tumor detection rate is insufficient, the dose may be gradually increased to a maximum of 5.0 mg/kg to determine the optimal dosage for effective tumor detection. This fluorescence spectroscopy during surgery may reveal additional lesions that remain undetected in preoperative assessments. The primary endpoint includes the correct diagnostic rate of tumor localization. The secondary endpoints include the measurement of the intraoperative ICG fluorescence spectral intensity in lung tumors, the assessment of the operability and safety of intraperitoneal ICG administrations, the measurement of the ICG fluorescence spectral intensity in surgical specimens, the comparison of the spectral intensity in lung tissues during collapse and expansion, the correlation between ICG camera images and fluorescence spectral intensity, and the comparison of fluorescence analysis results with histopathological findings. The trial has been registered in the jRCT Clinical Trials Registry under the code jRCTs011230037. Results and Conclusions: This trial aims to establish an effective methodology for localizing and diagnosing malignant lung tumors, thereby potentially improving surgical outcomes and refining treatment protocols.

Impact of pulmonary vein-first ligation during lobectomy on the postoperative survival and recurrence rates in patients with non-small cell lung cancer: a multicenter propensity score-matched study.

PURPOSE: Surgical manipulation of the lungs increases the number of circulating tumor cells and the subsequent risk of metastasis in patients with lung cancer. This study investigated whether or not ligating the tumor-draining pulmonary vein first during lobectomy could improve the prognosis of these patients. METHODS: We retrospectively evaluated patients who underwent curative lobectomy for solitary nonsmall-cell lung carcinoma between January 2012 and December 2016. We divided the patients into the vein-first group, in which all associated pulmonary veins were dissected and severed before cutting the pulmonary artery, bronchus, or pulmonary fissure, and the other procedure group. RESULTS: Overall, we included 177 and 413 patients in the vein-first and other procedure groups, respectively. Propensity score matching yielded 67 pairs of patients. The 5-year overall survival (85.6% [95% confidence interval, 77.3-94.8%] vs. 69.4% [58.7-81.9%], P = 0.03%) and recurrence-free survival (73.4% [63.3-85.1%] vs. 53.5% [42.5-67.3%], P = 0.02) were significantly better in the vein-first group than in the other procedure group. The cumulative recurrence rate at 5 years post-surgery was significantly lower in the vein-first group than in the other procedure group (21.7% vs. 38.3%, P = 0.04). CONCLUSION: Our study suggests that ligating the pulmonary vein first during lobectomy for lung cancer can improve the overall survival, recurrence-free survival, and cumulative recurrence rate.

A simple and safe surgical technique for nonpalpable lung tumors: One-stop Solution for a nonpalpable lung tumor, Marking, Resection, and Confirmation of the surgical margin in a Hybrid operating room (OS-MRCH).

When performing thoracoscopic partial resections of nonpalpable lung tumors such as ground-glass opacities (GGOs) and small tumors, detecting the location of the lesion and assessing the resection margins can be challenging. We have developed a novel method to ease this difficulty, the One-stop Solution for a nonpalpable lung tumor, Marking, Resection, and Confirmation of the surgical margin in a Hybrid operating room (OS-MRCH), which uses a hybrid operating room wherein the operating table is seamlessly integrated with cone-beam computed tomography (CBCT). We performed the OS-MRCH method on 62 nodules including primary lung cancer presenting with GGO. Identification of the lesion and confirmation of the margin were performed in 58 of the cases, while nodules were detected in all. The frequency of computed tomography (CT) scans performed prior to resection was one time in 51 cases, two times in eight cases, and ≥3 times in three cases. Additional resection was performed in two cases. The median operative time was 85.0 minutes, and the median pathological margin was 11.0 mm. The key advantages of this method are that all surgical processes can be completed in a single session, specialized skill sets are not required, and it is feasible to perform in any facility equipped with a hybrid operating room. To overcome its disadvantages, such as longer operating time and limited patient positioning, we devised various methods for positioning patients and for CT imaging of the resected specimens. OS-MRCH is a simple, useful, and practical method for performing thoracoscopic partial resection of nonpalpable lung tumors.

Esophageal perforation due to soft coagulation heat injury after right lower lobectomy: A case report.

INTRODUCTION: Soft coagulation is a hemostatic system of electrosurgical units that automatically regulates its output to avoid carbonization or incision. This system is widely used in invasive procedures, including thoracic surgery. Few reports exist on the harmful effects of these devices. Herein, we encountered a case of an esophagopleural fistula caused by soft coagulation. PRESENTATION OF CASE: A 74-year-old man with a history of bladder cancer was diagnosed with a tumor in the right lower lung lobe 2.5 cm in diameter. A thoracoscopic right lower lobectomy with lymph node dissection was performed. During surgery, hemostasis using soft coagulation was performed on the right wall of the lower esophagus. Eight days after surgery, thoracoscopic empyema curettage and drainage were performed. Three days after the second surgery, an esophageal fistula was identified. Suturing for the esophageal fistula and omentoplasty were performed. Suture failure occurred and an esophagobronchial fistula developed after the third surgery, which was reduced by drainage, antibiotics, and enteral nutrition. The fistula was finally addressed by fibrin glue filling in its cavity. DISCUSSION: Soft coagulation helps manage hemostasis and contributes to safe surgery. However, it may cause severe complications owing to the unpredictable spread of heat denaturation. It is suspected that delayed esophageal perforation was caused by an unnoticed heat injury to the deeper layer of the esophageal wall. CONCLUSION: There have been no reports of esophagus injury caused by soft coagulation exept for our experience. Although soft coagulation is a useful device owing to its excellent hemostatic capacity, the spread of heat denaturation may cause unpredictable tissue damage. Extra caution should be observed when using this device for hemostasis.

Developing a Virtual Reality Simulation System for Preoperative Planning of Robotic-Assisted Thoracic Surgery.

Background. Robotic-assisted thoracic surgery (RATS) is now standard for lung cancer treatment, offering advantages over traditional methods. However, RATS's minimally invasive approach poses challenges like limited visibility and tactile feedback, affecting surgeons' navigation through com-plex anatomy. To enhance preoperative familiarization with patient-specific anatomy, we devel-oped a virtual reality (VR) surgical navigation system. Using head-mounted displays (HMDs), this system provides a comprehensive, interactive view of the patient's anatomy pre-surgery, aiming to improve preoperative simulation and intraoperative navigation. Methods. We integrated 3D data from preoperative CT scans into Perspectus VR Education software, displayed via HMDs for in-teractive 3D reconstruction of pulmonary structures. This detailed visualization aids in tailored preoperative resection simulations. During RATS, surgeons access these 3D images through Tile-ProTM multi-display for real-time guidance. Results. The VR system enabled precise visualization of pulmonary structures and lesion relations, enhancing surgical safety and accuracy. The HMDs offered true 3D interaction with patient data, facilitating surgical planning. Conclusions. VR sim-ulation with HMDs, akin to a robotic 3D viewer, offers a novel approach to developing robotic surgical skills. Integrated with routine imaging, it improves preoperative planning, safety, and accuracy of anatomical resections. This technology particularly aids in lesion identification in RATS, optimizing surgical outcomes.

Induction of Oxidative Stress in Sirtuin Gene-Disrupted Ashbya gossypii Mutants Overproducing Riboflavin.

AgHST1 and AgHST3 genes encode sirtuins that are NAD+-dependent protein deacetylases. According to previous reports, their disruption leads to the overproduction of riboflavin in Ashbya gossypii. In this study, we investigated the potential causes of riboflavin overproduction in the AgHST1Δ and AgHST3Δ mutant strains of A. gossypii. The generation of reactive oxygen species was increasd in the mutants compared to in WT. Additionally, membrane potential was lower in the mutants than in WT. The NAD+/NADH ratio in AgHST1Δ mutant strain was lower than that in WT; however, the NAD+/NADH ratio in AgHST3Δ was slightly higher than that in WT. AgHST1Δ mutant strain was more sensitive to high temperatures and hydroxyurea treatment than WT or AgHST3Δ. Expression of the AgGLR1 gene, encoding glutathione reductase, was substantially decreased in AgHST1Δ and AgHST3Δ mutant strains. The addition of N-acetyl-L-cysteine, an antioxidant, suppressed the riboflavin production in the mutants, indicating that it was induced by oxidative stress. Therefore, high oxidative stress resulting from the disruption of sirtuin genes induces riboflavin overproduction in AgHST1Δ and AgHST3Δ mutant strains. This study established that oxidative stress is an important trigger for riboflavin overproduction in sirtuin gene-disrupted mutant strains of A. gossypii and helped to elucidate the mechanism of riboflavin production in A. gossypii.

A Case of Pneumothorax Required Surgical Treatment as a Complication of Paclitaxel with Bevacizumab Treatment.

A 63-year-old woman had a history of neoadjuvant chemotherapy, mastectomy, and adjuvant endocrine therapy for 5 years before being diagnosed with recurrent lesions involving the right anterior chest wall, multiple lymph nodes, and pulmonary metastases. The patient was subsequently initiated on a paclitaxel and bevacizumab regimen. During this treatment, the patient complained of palpitations and malaise. Chest radiography revealed a left pneumothorax. Despite attempts at conservative treatment, the pneumothorax did not improve and a thoracoscopic approach was required. One of the metastatic tumors in the left lower lobe appeared to rupture, and this area was estimated to be the cause of air leak. The tumor was covered with a tissue seal sheet, and the patient's condition improved with no recurrence of pneumothorax. This case highlights the importance of early conversion to surgical treatment when conservative treatment for pneumothorax is unresponsive due to the potential side effects of bevacizumab. The findings of this case report may be of interest to oncologists, pulmonologists, and other healthcare professionals involved in the care of patients with breast cancer and pulmonary metastases who are undergoing bevacizumab chemotherapy.

Tumor-to-thoracic height ratio as an easy method to predict the feasibility of reduced-port video-assisted thoracic surgery for mediastinal lesions in children: a single-center experience.

In the last few decades, reduced-port video-assisted thoracic surgery (RP-VATS) has been developed to minimize surgical invasiveness. Nevertheless, VATS in children can occasionally be difficult because the lesion occupies a small thoracic cavity, limiting the working space. This study aimed to assess the feasibility of RP-VATS for the resection of mediastinal lesions in children in association with the tumor-to-thoracic height ratio (TTH ratio). We reviewed all patients aged ≤10 years who underwent resection for mediastinal lesions in our institute between January 2008 and August 2022. Patients who underwent diagnostic procedures were excluded from this study. The TTH ratio was calculated as tumor height divided by thoracic height. Seven patients in the RP-VATS group and six in the conventional procedures (multi-portal VATS or open surgery) group were included in this study. The TTH ratio was significantly lower in the RP-VATS group than in the conventional procedures group (median, 26.3% vs. 50.8%; P=0.007). The operating time (P=0.01) and duration of drainage (P=0.003) were significantly shorter and the blood loss (P=0.001) was significantly lower in the RP-VATS group than in the conventional procedures group. After adjusting for age, a lower TTH ratio was significantly associated with the completion of RP-VATS (odds ratio: 0.776; 95% confidence interval: 0.529-0.926; P=0.048). In conclusion, RP-VATS can be performed appropriately in carefully selected cases of pediatric mediastinal lesions. A low TTH ratio may predict the feasibility of RP-VATS. Further studies are warranted to determine the criteria for the indications of RP-VATS in children, so that more children can benefit from RP-VATS.

Lung adenocarcinoma with micropapillary and solid patterns: Recurrence rate and trends.

BACKGROUND: Lung adenocarcinomas with micropapillary pattern (MP) or solid pattern (SP) have poor prognosis with frequent postoperative recurrence. However, treatment strategies for these histological subtypes have not been established. This study examined the recurrence rates and patterns in patients with these histological subtypes. METHODS: Overall, 238 patients with lung adenocarcinoma who underwent radical resection were included. According to the histological subtypes, the patients were classified into three groups: neither MP nor SP (MP-/SP-), MP (MP+), and SP (SP+). The clinical and pathological characteristics and recurrence-free survival (RFS) were examined in each group. In addition, univariate and multivariate analyses were performed to investigate the recurrence factors. The site of recurrence, PD-L1 expression, and driver mutations were examined in patients with postoperative recurrence. RESULTS: The recurrence rates were significantly higher in the MP+ and SP+ groups (p = 0.01). The RFS was significantly shorter in the MP+ and SP+ groups (p < 0.001) than in the MP-/SP- group, especially in pStage 1A (p = 0.001). The relationship between recurrence and pathologic factors was significant for pleural, lymphatic, and vascular invasion, as well as MP in univariate analysis and only for MP in multivariate analysis. Most recurrences were distant metastases in the MP+ and SP+ groups. PD-L1 was highly expressed in recurrent SP+ cases. CONCLUSIONS: Early-stage lung adenocarcinoma with MP or SP frequently has postoperative recurrence. Prevention of distant metastases is important in these patients to improve prognosis, and aggressive postoperative chemotherapy may be considered.

High density and proximity of CD8+ T cells to tumor cells are correlated with better response to nivolumab treatment in metastatic pleural mesothelioma.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer. METHODS: A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD-L1 positive cells, cell density, and cell-to-cell distance were analyzed by multiplex immunofluorescence. RESULTS: PD-L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group. CONCLUSIONS: High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma.

A novel edge-marking method in pleural covering with video-assisted thoracic surgery.

Total pleural covering is implemented to reinforce the visceral pleura with surgical sheets. It has been adopted for diffuse cystic lung diseases such as lymphangioleiomyomatosis to prevent pneumothorax and has achieved good results. The procedure is technically demanding, because it is difficult to cover the entire visceral pleura without disarrangement and jamming of surgical sheets, especially during thoracoscopic surgery, where grasping of a wrong site might happen when unfolding the sheets. Herein, we report a technique to cover the entire pleura with dotted line folded sheets to ease the thoracoscopic procedure. We found that the use of this marking method made the procedure easier, with just a little ingenuity, because marking the edges of sheets with dashed lines clarifies the site that should be grasped, thus preventing the incidence of grasping the wrong part of the sheet. Pleural covering with dotted line folded surgical sheets is a useful method for reduced port thoracoscopic surgery.

Invasive thymoma metastases to the pancreas: A case report.

INTRODUCTION AND IMPORTANCE: Thymoma is the most common type of tumor that develops in the thymic epithelial cells. Although thymomas can invade surrounding organs in the chest cavity, extrathoracic metastasis is very rare, and little is known about the prognosis and effective treatments for such tumors. Herein, we report a case of an invasive thymoma metastasizing to the pancreas after incomplete resection. CASE PRESENTATION: A 47-year-old man presented to our hospital with an anterior mediastinal mass. Although a thymic tumor was suspected, complete resection was not achieved because the tumor had invaded the pulmonary artery trunk, superior pulmonary vein, and left brachiocephalic vein. The pathological diagnosis was a Type B3 thymoma. The patient underwent chemotherapy and radiotherapy after surgery. Three years after surgery, computed tomography indicated a pancreatic mass suggestive of pancreatic cancer. Distal pancreatectomy was performed after neoadjuvant chemotherapy and radiotherapy. The pancreatic mass was diagnosed as Type B3 thymoma metastasis. Thirteen months after surgery for the pancreatic lesion, the patient underwent resection of the bilateral lung metastases. CLINICAL DISCUSSION: To the best of our knowledge, only four cases of metastatic thymic tumors in the pancreas have been reported. All patients who underwent surgical resection for pancreatic metastasis survived for >6 months including our case. CONCLUSION: In cases of thymic tumors with metastasis to extra-thoracic organs, complete resection of the metastatic lesions can contribute to prolonged survival.

Dedifferentiated liposarcoma primary to the chest wall with spontaneous shrinking: report of a case.

An 80-year-old man presented to our emergency department complaining of a mass on the right side of his chest and pain in the right flank of his back. A chest computed tomography (CT) scan showed a relatively heterogenous oval-shaped tumor measuring 7.5 × 6.0 cm eroded to the 8th rib, with slightly dense fluid accumulation inside and calcification of the tumor wall. A 1-month follow-up CT scan showed spontaneous shrinkage of the tumor. The tumor was completely excised from the thoracic wall and the wall was reconstructed with a polytetrafluoroethylene mesh. Pathological examination showed coagulation necrosis in the chest wall tumor, but immunohistochemical staining revealed murine double minute 2- and Cyclin-dependent kinase 4-positive cells with irregular nuclear size and bizarre morphology. Therefore, dedifferentiated liposarcoma (DDLPS) was the final pathological diagnosis. Remarkable infiltration of CD8+ lymphocytes into the tumor was observed, along with a 90% positive ratio for programmed cell death-ligand 1. The patient has been followed-up for 1 year without any recurrence, despite not receiving any additional treatment. Liposarcoma is one of the most common types of soft tissue sarcomas; however, spontaneous regression of primary DDLPS arising from the chest wall is extremely rare. Herein, we report a case of DDLPS primary to the chest wall with spontaneous regression, probably due to a spontaneously induced T cell response.

Repeated photodynamic therapy mediates the abscopal effect through multiple innate and adaptive immune responses with and without immune checkpoint therapy.

In combination with immune checkpoint inhibitors, photodynamic therapy can induce robust immune responses capable of preventing local tumor recurrence and delaying the growth of distant, untreated disease (ie. the abscopal effect). Previously, we found that repeated photodynamic therapy (R-PDT) using porphyrin lipoprotein (PLP) as a photosensitizer, without the addition of an immune checkpoint inhibitor, can induce the abscopal effect. To understand why PLP mediated R-PDT alone can induce the abscopal effect, and how the addition of an immune checkpoint inhibitor can further strengthen the abscopal effect, we investigated the broader immune mechanisms facilitated by R-PDT and combination R-PDT + anti-PD-1 monoclonal antibody (αPD-1) in a highly aggressive, subcutaneous AE17-OVA mesothelioma dual tumor-bearing C57BL/6 mice. We found a 46.64-fold and 61.33-fold increase in interleukin-6 (IL-6) after R-PDT and combination R-PDT + αPD-1 relative to PBS respectively, suggesting broad innate immune activation. There was a greater propensity for antigen presentation in the spleen and distal, non-irradiated tumor draining lymph nodes, as dendritic cells and macrophages had increased expression of MHC class II, CD80, and CD86, after R-PDT and combination R-PDT + αPD-1. Concurrently, there was a shift in the proportions of CD4+ T cell subsets in the spleen, and an increase in the frequency of CD8+ T cells in the distal, non-irradiated tumor draining lymph nodes. While R-PDT had an acceptable safety profile, combination R-PDT + αPD-1 induced 1.26-fold higher serum potassium and 1.33-fold phosphorus, suggestive of mild laboratory tumor lysis syndrome. Histology revealed an absence of gross inflammation in critical organs after R-PDT and combination R-PDT + αPD-1 relative to PBS-treated mice. Taken together, our findings shed light on how the abscopal effect can be induced by PDT and strengthened by combination R-PDT + αPD-1, and suggests minimal toxicities after R-PDT.

Optimization of thrombolytic dose for treatment of pulmonary emboli using endobronchial ultrasound-guided transbronchial needle injection.

OBJECTIVE: Severe pulmonary embolism is often managed with thrombolysis. We sought to determine whether endobronchial ultrasound (EBUS)-guided transbronchial thrombolysis remained effective at lower alteplase doses, with the goal of minimizing potential bleeding risk. METHODS: Yorkshire pigs were anesthetized and ventilated. Preformed autologous blood clots were administered into bilateral pulmonary arteries via EBUS-guided transbronchial injection. After documenting baseline clot sizes, alteplase was injected into the clots using a 25-gauge transbronchial needle and clot dissolution was monitored over 30 minutes. The study was performed in 2 phases. First, alteplase doses of 5 and 12.5 mg were evaluated. These results informed dose selection for the second phase. Results were compared with 25-mg dose data using EBUS from a previous study. RESULTS: In the first phase, 3 clots were evaluated. Distilled water, 5 mg, and 12.5 mg alteplase were administered. The dissolved clot volume (Vdis) and percentage clot volume loss (Rdis) were -10.9, 111.6, and 160.3 mm3, and -1.6%, 11.0%, and 59.3%, respectively. In the second phase, alteplase doses of 5, 10, and 15 mg were evaluated in 12 clots across 6 pigs. The Vdis were 247.5 mm3 (Rdis, 20.1%), 910.8 mm3 (Rdis, 80.9%), and 798.3 mm3 (Rdis, 76.0%) for 5, 10, and 15 mg alteplase, respectively. Remakably reduced performance was observed with 5 mg alteplase versus 10 mg (Vdis: P < .001, Rdis: P < .001), and 15 mg (Vdis: P = .004; Rdis: P < .001). No complications were observed. CONCLUSIONS: Alteplase doses ≥10 mg were optimal for EBUS-guided transbronchial thrombolysis. This technique might represent an effective alternative therapy for central pulmonary embolism.

Parietal pleural small holes found in patients with primary spontaneous pneumothorax associated with relatively mild chest wall flatness: a retrospective study.

Background: During surgery for spontaneous pneumothorax, parietal pleural small holes (PPSHs) are occasionally found around the apex of the intrapleural space; however, this has not been well recognized. Additionally, chest wall flatness is usually observed in patients with primary spontaneous pneumothorax (PSP) and PPSHs. This study aimed to investigate the prevalence of PPSH and evaluate the characteristics of patients with PPSH. We also investigated the degree of chest wall flatness in patients with PPSHs. Methods: We retrospectively reviewed all patients who underwent thoracoscopic surgery for pneumothorax at our department between April 2014 and May 2021. A propensity-matched analysis was used to compare the characteristics of patients with and without PPSH. Results: A total of 490 patients were enrolled in this study. PPSH was found in 45 of 297 (15.2%) patients with PSP and one of 193 (0.5%) patients with secondary pneumothorax. PSP was independently associated with the presence of PPSH after adjusting for age and sex [primary/secondary, odds ratio (OR) =34.3, 95% confidence interval (CI): 4.7-250.9; P<0.001]. Among patients with PSP, the flatness of the chest wall in patients with PPSH was not as severe as that in patients without PPSH {thoracic anteroposterior diameter (APDT) to transverse diameter (TDT) ratio; with PPSH: median =0.517 [interquartile range (IQR) =0.480-0.554] vs. without PPSH: median =0.487 (IQR =0.463-0.529; P=0.031)} after propensity score matching. Conclusions: PPSH is found in a non-negligible proportion of patients with PSP, and patients with PPSHs show a relatively mild flat chest among patients with PSP. Clinicians should be aware of PPSH, and further understanding of this condition may contribute to a better understanding of PSP.

Broadly Applicable and Comprehensive Synthetic Method for N-Alkyl-Rich Drug-like Cyclic Peptides.

We report a versatile and durable method for synthesizing highly N-alkylated drug-like cyclic peptides. This is the first reported method for synthesizing such peptides in parallel with a high success rate and acceptable purity that does not require optimizations for a particular sequence. We set up each reaction condition by overcoming the following issues: (1) diketopiperazine (DKP) formation, (2) insufficient peptide bond formation due to the steric hindrance of the N-alkylated amino acid, and (3) instability of highly N-alkylated peptides under acidic conditions. Using this newly established method, we successfully synthesized thousands of cyclic peptides to explore the scope of this modality in drug discovery. We here demonstrate the syntheses of a hundred representative examples, including our first clinical N-alkyl-rich cyclic peptide (LUNA18) that inhibits an intracellular tough target (RAS), in 31% total yield and 97% purity on average after 23 or 24 reaction steps.

Patterns and predictors of site-specific recurrence in cervical cancer after radical hysterectomy.

AIM: This study examines patterns and predictors of site-specific recurrence to explore the causes of local recurrence of cervical cancer. METHODS: Radical hysterectomy was performed in 121 patients (stage IB-IIB). Nerve-sparing was performed whenever possible. The first recurrence in local, regional, and distant areas was examined. We investigated the possibility of nerve involvement in local recurrence, focusing on paravaginal tissues containing the pelvic plexus. We provide Supporting Information on local recurrence in the paravaginal area. RESULTS: Local recurrence was an independent event from regional or distant recurrence. Local recurrence was seen only in high-risk patients, while regional and distant recurrences were not or less related to the risk category. The independent risk factors by logistic regression for local, regional, and distant recurrence were parametrial invasion, vaginal invasion, and lymph node metastasis, respectively. Local recurrence showed a comparable or more significant negative impact on survival than distant recurrence. Among seven patients with local recurrences, five had a recurrence in the paravagina. The rate of paravaginal recurrence was one in 76 early-stage and four in 45 locally advanced diseases. Four sites of paravaginal recurrence occurred on the nerve-sparing side and two on the non-nerve-sparing side. Supporting Information demonstrated histological evidence of perineural spread into the pelvic plexus and perineural invasion of the primary tumor. CONCLUSIONS: A high percentage of local recurrences are in paravaginal tissue containing the pelvic plexus. The causal association of nerve-sparing surgery and perineural invasion with local recurrence needs to be investigated in large prospective studies.