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A growth cone is a highly motile tip of an extending axon that is crucial for neural network formation. Three-dimensional-structured illumination microscopy, a type of super-resolution light microscopy with a resolution that overcomes the optical diffraction limitation (ca. 200 nm) of conventional light microscopy, is well suited for studying the molecular dynamics of intracellular events. Using this technique, we discovered a novel type of filopodia distributed along the z-axis ("z-filopodia") within the growth cone. Z-filopodia were typically oriented in the direction of axon growth, not attached to the substratum, protruded spontaneously without microtubule invasion, and had a lifetime that was considerably shorter than that of conventional filopodia. Z-filopodia formation and dynamics were regulated by actin-regulatory proteins, such as vasodilator-stimulated phosphoprotein, fascin, and cofilin. Chromophore-assisted laser inactivation of cofilin induced the rapid turnover of z-filopodia. An axon guidance receptor, neuropilin-1, was concentrated in z-filopodia and was transported together with them, whereas its ligand, semaphorin-3A, was selectively bound to them. Membrane domains associated with z-filopodia were also specialized and resembled those of lipid rafts, and their behaviors were closely related to those of neuropilin-1. The results suggest that z-filopodia have unique turnover properties, and unlike xy-filopodia, do not function as force-generating structures for axon extension.
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The understanding of supramolecular chirality in self-assembled molecular networks (SAMNs) on surfaces generates a lot of interest because of its relation to the production of chiral sensors, reactors, and catalysts. We herein report the adsorption of a prochiral solvent molecule in porous SAMNs formed by a chiral dehydrobenzo[12]annulene (cDBA) derivative. Through the prochirality recognition of a solvent molecule, the supramolecular chirality of the SAMN is switched: the cDBA exclusively forms a counter-clockwise pore through co-adsorption of the solvent molecule in prochiral 1,2,4-trichlorobenzene, while in 1-phenyloctane it produces the opposite chiral, clockwise pore. The prochirality recognition of the solvent molecule in the chiral SAMN pores is attributed to the adaptable conformational changes of the chiral chains of the cDBA molecule.
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Identifying the kinematic and behavioral variables of prey that influence evasion from predator attacks remains challenging. To address this challenge, we have developed an automated escape system that responds quickly to an approaching predator and pulls the prey away from the predator rapidly, similar to real prey. Reaction distance, response latency, escape speed and other variables can be adjusted in the system. By repeatedly measuring the response latency and escape speed of the system, we demonstrated the system's ability to exhibit fast and rapid responses while maintaining consistency across successive trials. Using the live predatory fish species Coreoperca kawamebari, we show that escape speed and reaction distance significantly affect the outcome of predator-prey interactions. These findings indicate that the developed escape system is useful for identifying kinematic and behavioral features of prey that are critical for predator evasion, as well as for measuring the performance of predators.
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Reação de Fuga , Comportamento Predatório , Animais , Reação de Fuga/fisiologia , Fenômenos Biomecânicos , Automação , Tempo de Reação/fisiologiaRESUMO
BACKGROUND: HER2-expressing salivary gland carcinoma (SGC) is associated with poor prognosis. Trastuzumab deruxtecan (T-DXd, DS-8201) has shown evidence of antitumor activity for several HER2-expressing solid tumors in multiple studies. This study aimed to present the efficacy and safety of T-DXd in patients with HER2-expressing SGC from a pooled analysis. METHODS: Patients with HER2-expressing SGC were pooled from two phase I, open-label studies of T-DXd: a two-phase, multiple-dose, first-in-human study (NCT02564900) and a single-sequence crossover drug-drug interaction study (NCT03383692). Endpoints included efficacy (objective response rate [ORR], duration of response [DoR] and progression-free survival [PFS]) and safety. RESULTS: This pooled analysis included 17 patients with SGC (median age: 57 years; male: 88.2%); median (range) follow-up duration was 12.0 (2.3-|34.8) months. Among these patients, 14 had received prior HER2-targeted agents and 13 had undergone prior radiotherapy. The investigator-assessed confirmed ORR was 58.8% (95% confidence interval [CI], 32.9-|81.6). The median (95% CI) DoR and PFS were 17.6 months (4.0 to not evaluable [NE]) and 20.5 months (11.1-NE), respectively. All 17 patients reported treatment-emergent adverse events (TEAEs); 76.5% reported TEAEs of grade ≥3. The most common TEAEs were decreased appetite (94.1%), nausea (88.2%) and neutrophil count decreased (76.5%). Of the 17 patients, five (29.4%) reported adjudicated drug-related interstitial lung disease (grade 1, n = 3; grade 2, n =1; grade 3, n = 1). CONCLUSION: The results of this pooled analysis provide evidence that clinical benefit is achievable with T-DXd in patients with HER2-expressing SGC. CLINICAL TRIAL INFORMATION: FIH study, NCT02564900; DDI study, NCT03383692.
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Camptotecina , Carcinoma , Imunoconjugados , Trastuzumab , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Camptotecina/uso terapêutico , Camptotecina/análogos & derivados , Carcinoma/tratamento farmacológico , Imunoconjugados/efeitos adversos , Imunoconjugados/uso terapêutico , Receptor ErbB-2/metabolismo , Glândulas Salivares/metabolismo , Trastuzumab/efeitos adversos , Trastuzumab/uso terapêutico , FemininoRESUMO
BACKGROUND: Esophageal squamous cell carcinoma is characterized by field cancerization, wherein multiple cancers occur in the esophagus, head and neck, and stomach. Synchronous esophageal and colorectal cancers are also encountered with a certain frequency. A good prognosis can be expected if the tumors in both locations can be safely and completely removed. For patients with multiple cancers that occur simultaneously with esophageal cancer, it is necessary to perform a staged operation, taking into consideration the associated surgical invasiveness. It is also necessary to select multidisciplinary treatment depending on the degree of progression of the multiple lesions. We report our rare experience with a staged operation for a patient with synchronous advanced cancers of the esophagus and cecum who had previously undergone total gastrectomy with reconstruction by jejunal interposition for gastric cancer. CASE PRESENTATION: A 71-year-old man with a history of reconstruction by jejunal interposition after total gastrectomy was diagnosed as having multiple synchronous esophageal and cecal cancers. After neoadjuvant chemotherapy, we performed a planned two-stage operation, with esophagectomy and jejunostomy in the first stage and ileocecal resection and jejunal reconstruction with vascular anastomosis in the second. Postoperatively, the patient was relieved without major complications, and both tumors were amenable to curative pathologic resection. CONCLUSIONS: Our procedure reported here may be recommended as an option for staged resection and reconstruction in patients with simultaneous advanced esophageal and cecal cancer after total gastrectomy.
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Neoplasias do Ceco , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Masculino , Humanos , Idoso , Neoplasias Esofágicas/cirurgia , Gastrectomia , Anastomose CirúrgicaRESUMO
INTRODUCTION: Reconstructed gastric tube ulcers are common complications of esophagectomy. When the pericardium is penetrated, digestive juices can cause severe cardiac inflammation, leading to an extremely poor prognosis. We report the first case of pericardial penetration of a constructed stomach tube via the posterior mediastinal route and the first use of subxiphoid pericardial drainage and continuous irrigation lavage. PRESENTATION OF CASE: This case involved a 50-year-old woman who underwent an esophagectomy for esophageal cancer nine years prior with gastric tube reconstruction via the posterior mediastinal route. She developed pericardial penetration due to a gastric tube ulcer. Her respiratory and circulatory condition worsened, and pericardial drainage and a prophylactic tracheostomy were performed to prevent septic shock. A 5-cm longitudinal incision was made in the epigastric region, and a 4-cm T-shaped incision was made through the pericardium. Two double-lumen drainage tubes were placed in the anterior and posterior pericardium, and continuous irrigation was initiated via each tube. We successfully treated the patient without complications using subxiphoid pericardial drainage and continuous irrigation lavage, and she was discharged on postoperative day 23. DISCUSSION: We presented this case to discuss surgical techniques and optimal treatment strategies. CONCLUSION: Subxiphoid pericardial drainage and continuous irrigational lavage are effective for pericardial penetration of a constructed stomach tube via the posterior mediastinal route.
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INTRODUCTION: Dermadrome is a term coined by combining the words "dermatology" and "syndrome," and it refers to dermatological symptoms that reflect visceral lesions. PRESENTATION OF CASE: Herein, we present the case of an 83-year-old female patient who presented with generalized blistering and erythema during treatment for acute pancreatitis. She was referred to our dermatology department with worsening erythema, although the acute pancreatitis improved. The cause of the erythema was suspected to be drug-induced, infectious, or related to collagen disease; however, the exact cause was unknown. Computed tomography and endoscopic ultrasonography findings revealed a mixed-type intraductal papillary mucinous neoplasm (IPMN). Refractory erythema was suspected to have been caused by a dermadrome due to IPMN. Consequently, she was referred to our department. The main pancreatic duct was dilated along its entire length, and tumor extension was difficult to determine; therefore, a total pancreatectomy was performed. The postoperative course was uneventful, and erythema gradually improved. The histopathological evaluation indicated high-grade dysplasia of the IPMN. DISCUSSION: The patient's skin rash, which did not improve with treatment that included high-dose steroids, began to improve after surgery, and the disease was thought to be a dermadrome caused by IPMN. CONCLUSION: We believe that this is the first reported case of IPMN with a dermadrome that resolved after a total pancreatectomy.
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BACKGROUND/AIM: Progress has been made in a triplet preoperative chemotherapy regimen for advanced esophageal cancer. We performed a preliminary investigation of the radiomics features of pathological lymph node metastasis after neoadjuvant chemotherapy using dual-energy computed tomography (DECT). PATIENTS AND METHODS: From January to December 2022, 36 lymph nodes from 10 patients with advanced esophageal cancer who underwent contrast-enhanced DECT after neoadjuvant chemotherapy and radical surgery in our department were studied. Radiomics features were extracted from iodine-based material decomposition images at the portal venous phase constructed by DECT using MATLAB analysis software. Receiver operating characteristic (ROC) analysis and cut-off values were determined for the presence or absence of pathological metastasis. RESULTS: ROC for the short axis of the pathologically positive lymph nodes showed an AUC of 0.713. Long run emphasis (LRE) within gray-level run-length matrix (GLRLM) was confirmed with a high AUC of 0.812. Sensitivity and specificity for lymph nodes with a short axis >10 mm were 0.222 and 1, respectively. Sensitivity and specificity for LRE within GLRLM were 0.722 and 0.833, respectively. Sensitivity and specificity for small zone emphasis (SZE) within gray-level size zone matrix (GLSZM) were 0.889 and 0.667, and zone percentage (ZP) values within GLSZM were 0.722 and 0.778, respectively. Discrimination of existing metastases using radiomics showed significantly higher sensitivity compared to lymph node short axis >10 mm (odds ratios of LRE, SZE, and ZP: 9.1, 28, and 9.1, respectively). CONCLUSION: Evaluation of radiomics analysis using DECT may enable a more detailed evaluation of lymph node metastasis after neoadjuvant chemotherapy.
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Neoplasias Esofágicas , Radiômica , Humanos , Metástase Linfática/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Tomografia Computadorizada por Raios X/métodos , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Estudos RetrospectivosRESUMO
Owing to advances in cancer treatment and the diversification of treatment methods, cancer-associated thrombosis is increasing. Cancer can cause blood clots by activating the blood clotting system, increasing clotting factors through inflammation, reducing blood flow due to immobilization and damaging blood vessels through treatments such as chemotherapy. In clinical practice, superior mesenteric vein (SMV) thrombosis is occasionally observed in patients with cancer; however, certain cases of asymptomatic thrombosis can be serious. In the present case, a 71-year-old woman underwent laparoscopic high anterior resection for colorectal cancer. The patient received capecitabine as postoperative adjuvant chemotherapy for 6 months. Contrast-enhanced CT after the completion of chemotherapy revealed a sizable thrombus in the SMV. The thrombus occupied the SMV lumen without evident intestinal ischemia. D-dimer levels were elevated. Since the patient remained asymptomatic, edoxaban (30 mg/day) was administered in an outpatient setting. Six months later, contrast-enhanced CT confirmed thrombus resolution. No hemorrhagic events were observed during edoxaban treatment. In conclusion, cancer and chemotherapy are risk factors for thrombosis, indicating that regular D-dimer measurements may be necessary during cancer treatment. In addition, edoxaban may be an effective therapeutic tool for SMV thrombosis during chemotherapy for cancer.
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BACKGROUND: Situs inversus totalis (SIT) is a rare congenital condition that involves complete transposition (right to left reversal) of the visceral organs. Laparoscopic surgery can be challenging because of the mirror-image anatomy. We describe a surgical innovation in laparoscopic surgery for SIT. CASE PRESENTATION: A 41-year-old man with SIT was diagnosed with an appendiceal tumor and underwent laparoscopic-assisted ileocecal resection. Preoperatively, we evaluated anatomical variations using 3D-computed tomography and simulated mirror images by watching flipped videos of patients with normal anatomy undergoing similar operations. During the operation, port placement and the surgeons' standing positions were reversed. Additionally, two monitors were placed at the patient's head, with one monitor showing original images, and the other showing flipped images that looked the same as the normal anatomy. We checked the range of the mobilized region and important anatomical structures by watching the flipped monitor as needed. The patient's postoperative course was uneventful. CONCLUSIONS: Due to the complexities of laparoscopic surgery for SIT, preoperative preparation and surgical innovation are necessary for safe surgery. Several suggestions have been made to understand anatomical anomalies and improve operability; however, surgeons must focus on the mirror-image anatomy throughout the operation. Therefore, the use of intraoperative flipped monitor will be helpful for surgeons in reducing the risk of anatomical misidentification.
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Patients with oligometastases show distant relapse in only a limited number of regions. Local therapy such as surgical resection, radiotherapy, chemoradiotherapy, and radiofrequency ablation for the relapsed sites may thus improve patient survival. Oligometastases are divided into oligo-recurrence and sync-oligometastases. Oligo-recurrence indicates a primary lesion that is controlled, and sync-oligometastases indicate a primary lesion that is not controlled. The management of oligo-recurrence and sync-oligometastases in esophageal squamous cell carcinoma has not been clearly established, and treatment outcomes remain equivocal. We reviewed 14 articles, including three phase II trials, that were limited to squamous cell carcinoma. Multimodal treatment combining surgical resection and chemoradiotherapy for oligo-recurrence of esophageal squamous cell carcinoma appears to be a promising treatment. With the development of more effective chemotherapy and regimens that combine immune checkpoint inhibitors, it will become more likely that sync-oligometastases that were unresectable at the initial diagnosis can be brought to conversion surgery. Currently, a randomized, controlled phase III trial is being conducted in Japan to compare a strategy for performing definitive chemoradiotherapy and, if necessary, salvage surgery with a strategy for conversion surgery in patients who can be resected by induction chemotherapy.
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BACKGROUND/AIM: A three-dimensional network constructed using glycocalyx (GCX) extends throughout the cancer cell nest in human colorectal cancer (CRC). GCX was found to be closely related to cancer. We examined the prognostic correlation and potential of syndecan-1 (SDC1), a representative proteoglycan of GCX, as a biomarker. PATIENTS AND METHODS: We analyzed SDC1 in the transcriptomic profiles of a major publicly available CRC cohort from The Cancer Genome Atlas (TCGA) using a computational algorithm. We investigated serum SDC1 levels preoperatively and on postoperative day seven in 48 patients with stage I-III CRC who underwent surgery during July-December 2019 at Gifu University Hospital. RESULTS: For TCGA, no significant differences existed between the high and low SDC1 expression groups regarding disease-free, disease-specific, and overall survival for stage I-III, and only overall survival for stage IV was significantly different. In our study, among the 48 patients, 17 (no recurrence), 13 (1 recurrence), and 18 (10 recurrences) had stage I-III, respectively. Preoperative and postoperative day 7 SDC1 levels for patients with stage I-III were 10.7±2.3 and 9.9±3.1 ng/ml (p=0.40), 11.1±1.7 and 10.1±0.8 ng/ml (p=0.07), and 10.3±2.0 and 9.5±1.4 ng/ml (p=0.15), respectively. In stage II and III, patients were divided into two groups according to differences between preoperative and postoperative SDC1 levels (SDC1pre-pro). SDC1pre-pro ≤0 group significantly prolonged disease-free survival compared with SDC1pre-pro >0 group (p=0.048). CONCLUSION: Dynamic change in serum SDC1 levels serves as a prognostic biomarker for stage II and III colorectal cancer.
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Neoplasias Colorretais , Sindecana-1 , Humanos , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Prognóstico , Sindecana-1/sangueRESUMO
BACKGROUND: Advances in chemotherapy have increased clinical experience with conversion surgery for inoperable advanced gastric cancer. This report describes three patients with unresectable gastric cancer accompanied by multiple liver metastases. In all three patients, nivolumab resolved the liver metastases and subsequent conversion surgery achieved a pathological complete response. CASE PRESENTATION: In Case 1, a 68-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX plus nivolumab. The patient completed 13 cycles; however, only nivolumab was continued for 3 cycles because of adverse events. Distal gastrectomy and partial hepatic resection were performed because of a significant reduction in the size of the liver metastases as observed on magnetic resonance imaging (MRI). In Case 2, a 72-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX. Because of the subsequent emergence of new liver metastases, the patient transitioned to ramucirumab plus paclitaxel as second-line therapy. Third-line therapy with nivolumab was initiated because of side effects. MRI revealed necrosis within the liver metastasis, and the patient underwent proximal gastrectomy and partial hepatectomy. In Case 3, a 51-year-old woman with clinical Stage IVB gastric cancer accompanied by multiple metastases of the liver and para-aortic lymph nodes began first-line therapy with SOX plus nivolumab. The patient completed 10 cycles; however, only nivolumab was continued for 5 cycles because of adverse events. Computed tomography showed a significant decrease in the size of the para-aortic lymph nodes, while MRI indicated the presence of a singular liver metastasis. Distal gastrectomy and partial hepatic resection were subsequently performed. In all three cases, MRI revealed the presence of liver metastases; however, pathological examination showed no viable tumor cells. CONCLUSIONS: We herein present three cases in which chemotherapy, including nivolumab, elicited a response in patients with multiple unresectable liver metastases, ultimately culminating in R0 resection through conversion surgery. Although MRI showed liver metastases, pathological analysis revealed no cancer, underscoring the beneficial impact of chemotherapy.
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The concept of oligometastasis is not yet fully established in the field of gastric cancer. However, metastatic lesions that are localized, technically resectable at diagnosis, present a certain response to preoperative chemotherapy, and present favorable survival outcomes with local treatments, sometimes in combination with chemotherapy, are recognized as oligometastasis in the field of gastric cancer. Oligometastasis is noted in European Society for Medical Oncology guidelines and Japanese gastric cancer treatment guidelines, and local treatment is mentioned as one of the pivotal treatment options for oligometastasis. Solitary liver metastasis or a small number of liver metastases; retroperitoneal lymph node metastasis, especially localized para-aortic lymph node metastasis; localized peritoneal dissemination; and Krukenberg tumor are representative types of oligometastasis in gastric cancer. The AIO-FLOT3 trial prospectively evaluated the efficacy of multimodal treatments for gastric cancer with oligometastasis, including surgical resection of primary and metastatic lesions combined with chemotherapy, confirming favorable survival outcomes. Two phase 3 studies are ongoing to investigate the efficacy of surgical resection combined with perioperative chemotherapy compared with palliative chemotherapy. Thus far, the evidence suggests that multimodal treatment for oligometastasis of gastric cancer is promising.
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Introduction: Patients with esophageal cancer who are in a poor general condition receive radiotherapy alone, but outcomes are often unsatisfactory. The aim of this study was to clarify recent outcomes of radiotherapy alone for esophageal cancer. Methods: Patients who underwent 50 Gy or more of radiotherapy without chemotherapy were retrospectively reviewed. Endpoints were overall survival (OS), disease-specific survival (DSS), local control (LC), and progression-free survival (PFS). Survival curves were drawn using the Kaplan-Meier method, and predictors were analyzed using the Cox proportional hazards model. Results: Sixty-nine patients were included. The median follow-up period was 17.9 months. The 5-year OS, DSS, LC, and PFS rates were 33.2%, 49.8%, 46.2%, and 16.8%, respectively. In the multivariate Cox proportional hazard model, clinical stage was a significant predictor for OS (hazard ratio [HR]: 4.42, 95% confidence interval [CI]: 1.80-11.17, p = 0.001), DSS (HR: 2.08, 95% CI: 1.43-3.12, p = 0.0001), LC (HR: 1.86, 95% CI: 1.28-2.74, p = 0.001), and PFS (HR: 1.65, 95% CI: 1.25-2.18, p = 0.0004). Radiation dose was a significant predictor for LC (HR: 0.87, 95% CI: 0.78-0.97, p = 0.018) and tumor location was a significant predictor for PFS (HR: 1.55, 95% CI: 1.10-2.19, p = 0.018). In subgroup analysis, the 5-year OS, DSS, LC, and PFS rates for stage I were 60.0%, 80.0%, 71.9%, and 46.1%, respectively. Conclusions: Stage, radiation dose, and tumor location are significant predictors for outcomes. Patients with stage I esophageal cancer can be cured by radiotherapy alone.
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Colorectal cancer (CRC) is the third most common cancer, and nearly half of CRC patients experience metastases. Oligometastatic CRC represents a distinct clinical state characterized by limited metastatic involvement, demonstrating a less aggressive nature and potentially improved survival with multidisciplinary treatment. However, the varied clinical scenarios giving rise to oligometastases necessitate a precise definition, considering primary tumor status and oncological factors, to optimize treatment strategies. This review delineates the concepts of oligometastatic CRC, encompassing oligo-recurrence, where the primary tumor is under control, resulting in a more favorable prognosis. A comprehensive examination of multidisciplinary treatment with local treatments and systemic therapy is provided. The overarching objective in managing oligometastatic CRC is the complete eradication of metastases, offering prospects of a cure. Essential to this management approach are local treatments, with surgical resection serving as the standard of care. Percutaneous ablation and stereotactic body radiotherapy present less invasive alternatives for lesions unsuitable for surgery, demonstrating efficacy in select cases. Perioperative systemic therapy, aiming to control micrometastatic disease and enhance local treatment effectiveness, has shown improvements in progression-free survival through clinical trials. However, the extension of overall survival remains variable. The review emphasizes the need for further prospective trials to establish a cohesive definition and an optimized treatment strategy for oligometastatic CRC.