Lymphangiogenesis after nonvascularized lymph node transplantation: Lymphangiographic findings in mice and minipigs.

The establishment of new connections after NVLNT (non-vascularized lymph node transplantation) is still poorly understood. The purpose of this study was to investigate lymphatic connections after NVLNT using lymphangiography. In a mice model, 40 mice were allocated to undergo NVLNT or sham surgery. On day 21 after NVLNT, the lymphatic vessels were observed on near-infrared fluorescence imaging with indocyanine green. In a minipig model, 12 minipigs underwent NVLNT. On day 14 after NVLNT, the transplanted lymph node and donor site were checked by ultrasound, and minipigs with viable transplanted LNs were allocated to lipiodol lymphangiography or MR lymphangiography groups. Transplanted LN engraftment was examined with immunohistochemical staining. After NVLNT in mice, the signal intensities in the popliteal region at 3 minutes and 5 minutes were higher in the transplanted side than the control side (21.3 ± 8.1 vs. 11.0 ± 4.6 at 3 minutes, 26.7 ± 6.8 vs. 19.7 ± 5.9 at 5 minutes), while in the sham group, there were no significant differences between sides. In minipigs, lipiodol lymphangiography (n = 5) showed Lipiodol accumulation in transplanted LNs with innumerable newly formed lymphatic vessels and lymphovenous shunts. MR lymphangiography (n = 5) showed higher enhancement on the transplanted side compared to the control side. Histology showed successful engraftment of transplanted LNs in 16 out of 20 (80%) mice and 9 out of 12 (75%) minipigs. Omnidirectional lymphangiogenesis forming a dense lymphatic network and spontaneous formation of lymphovenous shunts were shown after NVLNT.

The importance of sentinel lymph node diagnostic biopsy from the lateral neck compartment in the surgical treatment of papillary thyroid cance.

OBJECTIVES: The aim of our study is to determine whether mapping the lymphatic drainage and diagnostic excision of lymph nodes from lateral neck compartment is able to detect ultrasound unknown metastases in this compartment early and thus favorably affect the prognosis of patients with papillary thyroid cancer (PTC). BACKGROUND: Lymph node involvement in the lateral neck compartment is seen in 30-60 % of patients with PTC at the time of diagnosis and affects the prognosis of patients in terms of disease recurrence. METHODS: From June 2012 to December 2016, 154 patients with no evidence of lateral nodal involvement on imaging studies were treated with total thyroidectomy and central comparment neck dissection. A volume of 0.2 ml of Patent Blue dye was applied in the upper half of the thyroid gland with subsequent exposure of lymphatic drainage in the lateral compartment and 2-3 sentinel lymph nodes (SLN) were removed for frozen section (Group 1). In case of metastatic involvement, a lateral comparment neck dissection was performed. The reference groups were composed of a set of patients without detected lymphatic drainage (Group 2) and a set of patients who underwent lateral compartment neck dissection for preoperatively detected metastases in the lymph nodes (Group 3). The biochemical, structural and overall persistence of the disease at the time of administration of adjuvant radioiodine ablation was evaluated. RESULTS: The SLN identification rate was 95.45 %. In Group 1, a total of 32 patients had a positive SLN. Out of these, 24 patients had positive SLNs based on the analysis of frozen section, while in 8 patients, the positive diagnosis was confirmed through definitive histology. The comparison of data from the entire follow-up period in all three groups of patients revealed statistically significant differences in persistence of disease, namely in favor of Group 1. The percentage of reoperations for persistence and recurrence of disease was significantly lowest in Group 1 (2.04 %) compared to Groups 2 and 3 (6.94 % and 45.45 % respectively). CONCLUSION: The method is safe and sensitive for detecting unknown lymph node metastases in the lateral neck compartment, and may facilitate a decision to perform accurate surgical treatment of patients with PTC (Tab. 4, Fig. 2, Ref. 38).

Molybdenum target mammography-based prediction model for metastasis of axillary sentinel lymph node in early-stage breast cancer.

Sentinel lymph node (SLN) status is closely related to axillary lymph node metastasis in breast cancer. However, SLN biopsy has certain limitations due to invasiveness and diagnostic efficiency. This study aimed to develop a model to predict the risk of axillary SLN metastasis in early-stage breast cancer based on mammography, a noninvasive, cost-effective, and potential complementary way. Herein, 649 patients with early-stage breast cancer (cT1-T2) who received SLN biopsy were assigned to the training cohort (n = 487) and the validation cohort (n = 162). A prediction model based on specific characteristics of tumor mass in mammography was developed and validated with R software. The performance of model was evaluated by receiver operating characteristic curve, calibration plot, and decision curve analysis. Tumor margins, spicular structures, calcification, and tumor size were independent predictors of SLN metastasis (all P < .05). A nomogram showed a satisfactory performance with an AUC of 0.829 (95% CI = 0.792-0.865) in the training cohort and an AUC of 0.825 (95% CI = 0.763-0.888) in validation cohort. The consistency between model-predicted results and actual observations showed great Hosmer-Lemeshow goodness-of-fit (P = .104). Patients could benefit from clinical decisions guided by the present model within the threshold probabilities of 6% to 84%. The prediction model for axillary SLN metastasis showed satisfactory discrimination, calibration abilities, and wide clinical practicability. These findings suggest that our prediction model based on mammography characteristics is a reliable tool for predicting SLN metastasis in patients with early-stage breast cancer.

Lymphoscintigraphy as a Therapeutic Guidance Tool Can Improve Manual Lymphatic Drainage for the Physical Treatment of Patients with Upper Limb Lymphedema: Randomized Clinical Trial.

Background: The purpose of this study was to measure the effects of lymphoscintigraphically guided manual lymphatic drainage (LG-MLD) and to compare it with standardized manual lymphatic drainage (St-MLD). Materials and Methods: Fifty-two patients with lymphedema of the upper limb who underwent lymphoscintigraphy were randomly allocated into two groups. Following the phase of physical activity, the control group underwent two phases of St-MLD as the experimental group underwent a first phase of St-MLD followed by a second phase of LG-MLD. Areas of interest were then selected [in particular, dermal backflow (DBF) and axillary lymph nodes (LN)], radioactive activities were quantified for each of these areas. Results: If a first phase of St-MLD increased the LN activity by 28% on average, the findings indicated that for the second phase of DLM, LG-MLD was 19% more efficient than St-MLD in increasing LN activity. If a period of rest does not influence the lymph charge of DBF areas, physical activity leads to an average activity increase of 17%, whereas LG-MLD and St-MLD lead to an activity decrease of 11%. Conclusions: For patients with lymphedema, the findings indicate that MLD can increase the lymphatic flow toward the lymphatic nodes by 28% on average and can decrease the charge in the areas of DBF by 11% on average. Moreover, lymphoscintigraphy can be an important therapeutic tool because LG-MLD significantly increases lymphatic flow by 19% more than St-MLD. Concerning the areas of DBF, the LG-MLD and St-MLD decrease the charge in these areas with the same intensity.

Deep epigastric lymph nodes implication in patients' recurrence pattern after cytoreductive surgery in ovarian peritoneal metastases.

INTRODUCTION: Although complete cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) offers a good prognosis in patients with peritoneal metastasis of ovarian cancer (PMOC), recurrences are quite common. These recurrences can be intra-abdominal or systemic in nature. Our objective was to study and illustrate the global recurrence pattern in patients operated for PMOC, shedding light on a previously overlooked lymphatic basin at the level of the epigastric artery, the deep epigastric lymph nodes (DELN) basin. PATIENTS AND METHODS: This was a retrospective study including patients with PMOC who underwent surgery with curative-intent, from 2012 until 2018, at our cancer center, and who presented with any type of disease recurrence on follow-up. CT-scans, MRIs and PET-scans were reviewed in order to determine solid organs and lymph nodes (LN) recurrences. RESULTS: During the study period, 208 patients underwent CRS ± HIPEC, 115 (55.3%) presented with organ or lymphatic recurrence over a median follow-up of 81 months. Sixty percent of these patients had radiologically enlarged LN involvement. The pelvis/pelvic peritoneum was the most common intra-abdominal organ recurrence site (47%), while the retroperitoneal LN was the most common lymphatic recurrence site (73.9%). Previously overlooked DELN were found in 12 patients, with 17.4% implication in lymphatic basin recurrence patterns. CONCLUSION: Our study revealed the potential role of the DELN basin, previously overlooked in the systemic dissemination process of PMOC. This study sheds light on a previously unrecognized lymphatic pathway, as an intermediate checkpoint or relay, between the peritoneum, an intra-abdominal organ, and the extra-abdominal compartment.

Value of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration to Diagnose the Lung Nodules Related Enlarged Mediastinal Lymph Nodes.

Background: To investigate the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of lung nodules related enlarged mediastinal lymph nodes (MLNs). Methods: Clinical data of 108 patients with lung nodules related enlarged MLNs who underwent EBUS-TBNA in our single center were retrospectively analyzed from January 2020 to December 2021. The sensitivity and specificity of EBUS-TBNA in malignancy diagnosis were evaluated. Associations between ultrasonic image measurement indexes and malignancy diagnosis were explored. The receiver operating characteristic (ROC) curve of these indexes, the area under curve (AUC), and the corresponding cut-off values were calculated to predict malignant MLNs. Results: Sensitivity, specificity, and accuracy of EBUS-TBNA in the diagnosis of lung nodules related malignant MLNs were 89.47%, 100%, and 92.59%, respectively. There were significantly higher proportions of malignant MLNs with clear boundary, short diameter ≥1 cm, lower long to short diameter ratio, abundant flow of blood, and destructed medulla than that of benign ones (P < .05). According to ROC curve analysis, the cut-off value of short diameters for predicting malignant MLNs was 1.085 cm, and the AUC was 0.796 (95% confidence interval: 0.724-0.868, P < .001). Corresponding sensitivity and specificity were 61.36% and 80.00%, respectively. The cut-off value of the long to short diameter ratio for predicting malignancy was 1.405, and the AUC was 0.697 (95% confidence interval: 0.609-0.790, P < .001). Corresponding sensitivity and specificity were 70.00% and 71.97%, respectively. Conclusion: EBUS-TBNA has a satisfactory accuracy of lung nodules related MLNs diagnosis. Short diameters and long to short diameter ratio of lung nodules related MLNs in ultrasonic image may contribute to the prediction of malignant lymph nodes.

Tumor-Targeted Polydopamine-Based Nanoparticles for Multimodal Mapping Following Photothermal Therapy of Metastatic Lymph Nodes.

Purpose: Lymphadenectomy with lymph node (LN) mapping is essential for surgical removal of solid tumors. Existing agents do not provide accurate multimodal mapping and antitumor therapy for metastatic LNs; therefore, we fabricated a polydopamine (PDA) nanoparticle (NP)-based tumor-targeted LN mapping agent capable of multimodal mapping and guided photothermal therapy (PTT) for metastatic LNs. Materials and Methods: PDA NPs modified with polyethylene glycol (PEG) were obtained by polymerization under alkaline conditions. The PEG-PDA NPs were loaded with the circular tripeptide Arg-Gly-Asp (cRGD) to achieve tumor-targeting capacity and with the fluorescent dye IR820 and magnetic resonance imaging (MRI) contrast Gd(NH2)2 for in situ detection. The resulting cRGD-PEG-PDA@IR820/Gd(NH2)2 (cRGD-PPIG) NPs were tested for their biosafety and metastatic LN mapping ability. They were drained specifically into LNs and selectively taken up by gastric MKN45 cells via αvß3 integrin-mediated endocytosis. Results: This phenomenon enabled MR/optical/near-infrared fluorescence multimodal metastatic LN mapping, guiding the creation of accurate and highly efficient PTT for gastric cancer metastatic LNs in mice. Conclusion: In summary, we fabricated tumor-targeted cRGD-PPIG NPs with MR/optical/near-infrared fluorescence multimodal metastatic LN mapping capacity for surgery and efficient PTT guidance post-surgery.

Symptomatic isolated axillary lymph node sarcoidosis: an unusual presentation.

An 82-year-old woman admitted following a 4-week history of feeling unwell, abdominal pain and constipation. Initial investigations revealed severe hypercalcaemia with suppressed parathyroid hormone and elevated 1,25-dihydroxycholecalciferol. ACE was also raised. CT scans of the head, chest, abdomen and pelvis were normal. Fluorodeoxyglucose-positron emission tomography scan showed metabolically active right axillary lymphadenopathy which when biopsied under ultrasound guidance confirmed sarcoidosis. The patient was started on high-dose prednisolone with resolution of symptoms within 2 weeks. Isolated lymph node sarcoidosis is uncommon, and the reported usual sites are lymph nodes in the head and neck. Rarely has it been reported in the axillary lymph nodes.

Condition of Adrenergic Innervation Apparatus of the Thyroid Gland, Blood and Lymph Vessels, and Lymph Nodes during Correction of Hypothyrosis.

We used specific histochemical fluorescence-microscopic method of visualization of catecholamines to study adrenergic innervation of the thyroid gland tissue, blood vessels of the thyroid gland, cervical lymphatic vessel and lymph nodes in rats during correction of hypothyroidism with a bioactive formulation (Vozrozhdenie Plus balm with Potentilla alba L.). In experimental hypothyroidism, adrenergic innervation of the thyroid gland and the wall of the cervical lymph node, concentrated mainly along the arterial vessels and the cervical lymphatic vessel, retained its structural formations (plexuses and varicosities), but diffusion of catecholamines outside these formations was observed. Correction with the bioactive formulation restored of the contours of the nerve plexuses and varicosities and their brighter fluorescence in the thyroid gland and cervical lymphatic vessel and node. During correction of hypothyroidism with the bioactive formulation, reorganization of regional lymphatic vessels and nodes was more pronounced than reorganization of the thyroid gland.

Effect of contrast agent viscosity and massage on success of computed tomography lymphangiography with aqueous contrast for sentinel lymph node identification in healthy dogs.

Sentinel lymph node (SLN) evaluation is important for accurate cancer staging. Computed tomography (CT) lymphangiography with aqueous contrast is a feasible technique for SLN identification in dogs. Although most studies report success rates around 90%, success rates as low as 60% have been reported. One reason for low success rates may be the difference in viscosity of the various agents used in comparison to normal lymph viscosity. The objective of this study was to evaluate contrast agents of differing viscosities for use in CT lymphangiography for SLN identification and to determine the influence of massage on contrast flow rates. The hypothesis was that lower viscosity agents would have a higher success rate and faster time to identification of the SLN than higher viscosity agents and that massage would increase contrast flow rates. Dogs were anaesthetised and CT lymphangiography was performed with four contrast agents of differing viscosities in a randomized crossover design. Injections were made on the dorsal pes bilaterally on two study days and the popliteal lymph nodes were evaluated for contrast uptake. There was no significant difference in success of SLN identification or time to SLN identification among the four agents. Massage of the injection site increased rate of contrast flow through the lymphatics. No specific recommendation for one contrast agent over another can be made with these results. Massage is recommended to improve lymphatic flow when performing CT lymphangiography with aqueous contrast in dogs.

Intermediary clip placement to assist accurate axillary lymph node localization.

Localization of metastatic axillary lymph nodes in breast cancer patients is an increasingly common procedure performed by radiologists. In 2014, the National Comprehensive Cancer Network guidelines stated that "clinically positive axillary lymph node (s) should be sampled by FNA or core biopsy and clipped with image-detectable marker; clipped lymph nodes must be removed if FNA or core biopsy was positive prior to neoadjuvant therapy". Since then, multiple studies have further supported targeted axillary surgery after neoadjuvant chemotherapy (NAC), with excision of the clipped metastatic axillary node in addition to the sentinel node (s). Requests for image guided localization of clipped axillary nodes will continue to increase and likely become the standard of care. However, when lymph nodes have decreased in size after NAC, or when small deep lymph nodes are sampled, the clipped node can be difficult to identify under ultrasound at the time of localization. When the target node is questionable, we have found it valuable to place an intermediary clip, and use an axillary mammographic view to confirm this intermediary clip co-localizes with the intended target. With this confirmation, safe, accurate localization can then be performed. We describe 3 cases of intermediary clip placement facilitating successful localization of previously clipped axillary lymph nodes.

Quantitative MRI cell tracking of immune cell recruitment to tumors and draining lymph nodes in response to anti-PD-1 and a DPX-based immunotherapy.

DPX is a unique T cell activating formulation that generates robust immune responses (both clinically and preclinically) which can be tailored to various cancers via the use of tumor-specific antigens and adjuvants. While DPX-based immunotherapies may act complementary with checkpoint inhibitors, combination therapy is not always easily predictable based on individual therapeutic responses. Optimizing these combinations can be improved by understanding the mechanism of action underlying the individual therapies. Magnetic Resonance Imaging (MRI) allows tracking of cells labeled with superparamagnetic iron oxide (SPIO), which can yield valuable information about the localization of crucial immune cell subsets. In this work, we evaluated the use of a multi-echo, single point MRI pulse sequence, TurboSPI, for tracking and quantifying cytotoxic T lymphocytes (CTLs) and myeloid lineage cells (MLCs). In a subcutaneous cervical cancer model (C3) we compared untreated mice to mice treated with either a single therapy (anti-PD-1 or DPX-R9F) or a combination of both therapies. We were able to detect, using TurboSPI, significant increases in CTL recruitment dynamics in response to combination therapy. We also observed differences in MLC recruitment to therapy-draining (DPX-R9F) lymph nodes in response to treatment with DPX-R9F (alone or in combination with anti-PD-1). We demonstrated that the therapies presented herein induced time-varying changes in cell recruitment. This work establishes that these quantitative molecular MRI techniques can be expanded to study a number of cancer and immunotherapy combinations to improve our understanding of longitudinal immunological changes and mechanisms of action.

Unexpected radioactive iodine accumulation on whole-body scan after I-131 ablation therapy for differentiated thyroid cancer.

We retrospectively evaluated the frequency of unexpected accumulation of radioactive iodine on the post-therapy whole-body scan (Rx-WBS) after radioactive iodine (RAI) ablation therapy in patients with differentiated thyroid cancer (DTC). We searched our institutional database for Rx-WBSs of DTC patients who underwent RAI ablation or adjuvant therapy between 2012 and 2019. Patients with distant metastasis diagnosed by CT or PET/CT before therapy, and those had previously received RAI therapy were excluded. In total, 293 patients (201 female and 92 male, median age 54 years) were selected. Two nuclear medicine physicians interpreted the Rx-WBS images by determining the visual intensity of radioiodine uptake by the thyroid bed, cervical and mediastinal lymph nodes, lungs, and bone. Clinical features of the patients with and without the metastatic accumulation were compared by chi-square test and median test. Logistic regression analyses were performed to compare the association between the presence of metastatic accumulation and these clinical factors. Eighty-four of 293 patients (28.7%) showed metastatic accumulation. Patients with metastatic RAI accumulation showed a significantly higher frequency of pathological N1 (pN1) and serum thyroglobulin (Tg) > 1.5 ng/ml under TSH stimulation (p = 0.035 and p = 0.031, respectively). Logistic regression analysis indicated that a serum Tg > 1.5 ng/ml was significantly correlated with the presence of metastatic accumulation (odds ratio = 1.985; p = 0.033). In conclusion, Patients with Tg > 1.5 ng/ml were more likely to show metastatic accumulation. In addition, the presence of lymph node metastasis at the initial thyroid surgery was also associated with this unexpected metastatic accumulation.

Differentiation of benign and malignant lymph nodes in pediatric patients on ferumoxytol-enhanced PET/MRI.

The composition of lymph nodes in pediatric patients is different from that in adults. Most notably, normal lymph nodes in children contain less macrophages. Therefore, previously described biodistributions of iron oxide nanoparticles in benign and malignant lymph nodes of adult patients may not apply to children. The purpose of our study was to evaluate if the iron supplement ferumoxytol improves the differentiation of benign and malignant lymph nodes in pediatric cancer patients on 18F-FDG PET/MRI. Methods: We conducted a prospective clinical trial from May 2015 to December 2018 to investigate the value of ferumoxytol nanoparticles for staging of children with cancer with 18F-FDG PET/MRI. Ferumoxytol is an FDA-approved iron supplement for the treatment of anemia and has been used "off-label" as an MRI contrast agent in this study. Forty-two children (7-18 years, 29 male, 13 female) received a 18F-FDG PET/MRI at 2 (n=20) or 24 hours (h) (n=22) after intravenous injection of ferumoxytol (dose 5 mg Fe/kg). The morphology of benign and malignant lymph nodes on ferumoxytol-enhanced T2-FSE sequences at 2 and 24 h were compared using a linear regression analysis. In addition, ADCmean-values, SUV-ratio (SUVmax lesion/SUVmean liver) and R2*-relaxation rate of benign and malignant lymph nodes were compared with a Mann-Whitney-U test. The accuracy of different criteria was assessed with a receiver operating characteristics (ROC) curve. Follow-up imaging for at least 6 months served as the standard of reference. Results: We examined a total of 613 lymph nodes, of which 464 (75.7%) were benign and 149 (24.3%) were malignant. On ferumoxytol-enhanced T2-FSE images, benign lymph nodes showed a hypointense hilum and hyperintense parenchyma, while malignant lymph nodes showed no discernible hilum. This pattern was not significantly different at 2 h and 24 h postcontrast (p=0.82). Benign and malignant lymph nodes showed significantly different ferumoxytol enhancement patterns, ADCmean values of 1578 and 852 x10-6 mm2/s, mean SUV-ratios of 0.5 and 2.8, and mean R2*-relaxation rate of 127.8 and 84.4 Hertz (Hz), respectively (all p<0.001). The accuracy of ADCmean, SUV-ratio and pattern (area under the curve (AUC): 0.99; 0.98; 0.97, respectively) was not significantly different (p=0.07). Compared to these three parameters, the accuracy of R2* was significantly lower (AUC: 0.93; p=0.001). Conclusion: Lymph nodes in children show different ferumoxytol-enhancement patterns on MRI than previously reported for adult patients. We found high accuracy (>90%) of ADCmean, SUV-ratio, pattern, and R2* measurements for the characterization of benign and malignant lymph nodes in children. Ferumoxytol nanoparticle accumulation at the hilum can be used to diagnose a benign lymph node. In the future, the delivery of clinically applicable nanoparticles to the hilum of benign lymph nodes could be harnessed to deliver theranostic drugs for immune cell priming.

A Canine Model for Lymphangiography and Thoracic Duct Access.

OBJECTIVE: To evaluate the technical feasibility of intranodal lymphangiography and thoracic duct (TD) access in a canine model. MATERIALS AND METHODS: Five male mongrel dogs were studied. The dog was placed in the supine position, and the most prominent lymph node in the groin was accessed using a 26-gauge spinal needle under ultrasonography (US) guidance. If the cisterna chyli (CC) was not opacified by bilateral lymphangiography, the medial iliac lymph nodes were directly punctured and Lipiodol was injected. After opacification, the CC was directly punctured with a 22-gauge needle. A 0.018-in microguidewire was advanced through the CC and TD. A 4-Fr introducer and dilator were then advanced over the wire. The microguidewire was changed to a 0.035-in guidewire, and this was advanced into the left subclavian vein through the terminal valve of the TD. Retrograde TD access was performed using a snare kit. RESULTS: US-guided lymphangiography (including intranodal injection of Lipiodol [Guerbet]) was successful in all five dogs. However, in three of the five dogs (60%), the medial iliac lymph nodes were not fully opacified due to overt Lipiodol extravasation at the initial injection site. In these dogs, contralateral superficial inguinal intranodal injection was performed. However, two of these three dogs subsequently underwent direct medial iliac lymph node puncture under fluoroscopy guidance to deliver additional Lipiodol into the lymphatic system. Transabdominal CC puncture and cannulation with a 4-Fr introducer was successful in all five dogs. Transvenous retrograde catheterization of the TD (performed using a snare kit) was also successful in all five dogs. CONCLUSION: A canine model may be appropriate for intranodal lymphangiography and TD access. Most lymphatic intervention techniques can be performed in a canine using the same instruments that are employed in a clinical setting.

Conversion Surgery for Metastatic Pancreatic Mucinous Carcinoma Responsive to Systemic Chemotherapy with Modified FOLFIRINOX: A Case Report.

We report a case of metastatic pancreatic-head mucinous carcinoma (with multiple lymph node and bone metastases) and review the relevant literature. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was useful for diagnosis, and a satisfactory outcome was achieved after systemic chemotherapy with FOLFIRINOX followed by resection of the primary lesion as conversion surgery. The patient was a 55-year-old man. Hematological findings included elevated serum tumor marker levels: CEA 12.7 ng/mL, DUPAN-2 400 U/mL. Findings from several imaging modalities and EUS-FNA confirmed a clinicopathological diagnosis of metastatic pancreatic mucinous carcinoma with multiple bone and lymph node metastases. Five courses of modified FOIFIRINOX (m-FFX) were given as systemic chemotherapy, which had an antitumor effect. Subtotal stomach-preserving pancreaticoduodenectomy and extensive lymph-node dissection were thus performed. Histopathological analysis showed invasive ductal carcinoma, muc (pT3, pN1b, cM1). After surgery, the clinical course was notable for the absence of complications. Tegafur/gimeracil/oteracil (S-1) was started as maintenance adjuvant chemotherapy postoperatively, and no disease progression has been observed at 10 months after surgery.

Synthesis of an efficient far-red/near-infrared luminogen with AIE characteristics for in vivo bioimaging applications.

A selenium-containing FR/NIR AIE luminogen with efficient solid-state emission is reported. Its AIE dots exhibit high brightness, large Stokes shift, good biocompatibility and satisfactory photostability, making them the first selenium-containing FR/NIR nanoprobes with AIE characteristics for in vivo bioimaging applications with high contrast and a high penetration depth.

Structural and diffusion weighted MRI demonstrates responses to ibrutinib in a mouse model of follicular helper (Tfh) T-cell lymphoma.

Recent analyses of the genetics of peripheral T-cell lymphoma (PTCL) have shown that a large proportion of cases are derived from normal follicular helper (Tfh) T-cells. The sanroque mouse strain bears a mutation that increases Tfh cell number and heterozygous animals (Roquinsan/+) develop lymphomas similar to human Tfh lymphoma. Here we demonstrate the usefulness of Roquinsan/+ animals as a pre-clinical model of Tfh lymphoma. Long latency of development and incomplete penetrance in this strain suggests the lymphomas are genetically diverse. We carried out preliminary genetic characterisation by whole exome sequencing and detected tumor specific mutations in Hsp90ab1, Ccnb3 and RhoA. Interleukin-2-inducible kinase (ITK) is expressed in Tfh lymphoma and is a potential therapeutic agent. A preclinical study of ibrutinib, a small molecule inhibitor of mouse and human ITK, in established lymphoma was carried out and showed lymphoma regression in 8/12 (67%) mice. Using T2-weighted MRI to assess lymph node volume and diffusion weighted MRI scanning as a measure of function, we showed that treatment increased mean apparent diffusion coefficient (ADC) suggesting cell death, and that change in ADC following treatment correlated with change in lymphoma volume. We suggest that heterozygous sanroque mice are a useful model of Tfh cell derived lymphomas in an immunocompetent animal.

Semiconducting Perylene Diimide Nanostructure: Multifunctional Phototheranostic Nanoplatform.

Precision medicine requires noninvasive and accurate early diagnosis and individually appropriate treatments. Phototheranostics has been considered a frontier precision medical technology to provide rapid and safe disease localization and efficient cure. Harnessing the power of advanced nanomedicine with photonics, phototheranostics is rapidly developing and progressively becoming irreplaceable in modern medicine. Nanoscale semiconducting materials, such as inorganic semiconductors, organic conjugated polymers, and small molecules with photonic properties, have been extensively explored in medical imaging (fluorescence imaging, optical coherence tomography, and photoacoustic [PA] imaging) and phototherapy (photothermal, photodynamic, and photocontrolled combination therapies). In practical clinical applications, organic semiconducting materials, because of their biocompatibility and natural metabolism, are preferred over inorganic materials for phototheranostics. Supramolecular self-assembly is considered a significant method for preparing organic detachable and multifunctional phototheranostics, as supramolecular interactions, such as π-π interactions, hydrogen bonding, hydrophobic effects, and electrostatic interactions, are non-covalent and dynamic. Developing new and effective organic supramolecular phototheranostics requires exploration of well-designed basic building blocks with optical properties, understanding of the assembly at the nanoscale, and optimization of the phototheranostics with unique and distinctive multifunctional efficacy. In this Account, we summarize our recent work on the development of small molecular semiconducting perylene diimide (SPDI) for advanced phototheranostics. SPDI is modified to have strong near-infrared absorption beyond 700 nm by the push-pull electronic effect and owns the merits of remarkable photostability, large extinction coefficient, and high photothermal conversion efficiency. By hydrophilic modification, the amphiphile can self-assemble into a nanomicellar structure that allows PA imaging and can serve as a photothermal conversion agent. After theranostics delivery is achieved, this SPDI can be further functionalized for multimodality imaging and photothermally triggered multimodal synergistic therapy. Several well-designed asymmetric structures of SPDI can be obtained by stepwise modification of imides. It is noteworthy that the self-assembly of SPDI is controllable, allowing the preparation of different-sized spherical nanoparticles and rodlike nanoparticles and nanodroplets. For biomedical applications of SPDI phototheranostics (SPDIPTs), the size effect of SPDIPTs has been highlighted in lymph node mapping and cancer imaging. The PA properties and targeting peptide modification of SPDIPTs have brought about the ultrasensitive imaging of early thrombus. The supramolecular nanoconstructs of SPDIPTs further permit multimodality-imaging-guided cancer therapy. In brief, the design of SPDIPTs considers synthetic chemistry, supramolecular self-assembly, nanotechnology, and photonics. Furthermore, SPDIPTs have diverse biomedical applications and offer many opportunities for advancing nanomedicine.