Construction of a Novel Cascade Electrolysis-Heterocatalysis System by Using Zeolite-Encaged Ultrasmall Palladium Catalysts for H2 O2 Generation.

In situ generation of hydrogen peroxide (H2 O2 ) has attracted extensive attention, especially in water treatment. However, traditional anthraquinones can only produce high-concentration H2 O2 and its transportation and storage are not convenient and dangerous. Herein, an in situ and on-demand strategy to produce H2 O2 by using a cascade water electrolysis together with a heterocatalysis system is provided. Beginning with water, H2, and O2 can be generated via electrolysis and then react with each other to produce H2 O2 immediately on efficient zeolite-encaged ultrasmall Pd catalysts. Significantly, the H2 O2 generation rate in the optimized cascade system reaches up to 0.85 mol L-1 h-1 gPd -1 , overcoming most of the state-of-the-art catalysts in previous literature. The confinement effect of zeolites is not only beneficial to the formation of highly dispersed metal species, promoting the H2 O2 generation, but also inhibits the H2 O2 decomposition, enhancing the production yield of H2 O2 . In addition, the effect of electrolytes, sizes of Pd species, as well as zeolite acidity are also systematically studied. This work provides a new avenue for H2 O2 generation via a highly efficient cascade electrolysis-heterocatalysis system by using zeolite-supported metal catalysts. The high catalytic efficiency and green process for H2 O2 generation make it very promising for further practical applications.

Clinical response to adding pyrotinib to pembrolizumab and lenvatinib for HER2-positive advanced intrahepatic cholangiocarcinoma: a case report.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly lethal hepatobiliary cancer, and very few patients can undergo surgery. The prognosis of advanced ICC is poor, especially in patients who progress after first-line chemotherapy, with a median overall survival of less than 10 months. CASE PRESENTATION: A 64-year-old male was diagnosed with advanced intrahepatic cholangiocarcinoma with ERBB2 (HER2) 3 + amplification determined by tissue-based testing and confirmed by next-generation sequencing. The patient was treated with pyrotinib added to pembrolizumab and lenvatinib after progressing with pyrotinib and tegafur and responded very well with regression of the tumor on imaging as well as normalization of tumor marker levels without serious adverse events. PET-CT after 6 months of treatment showed a partial response. The progression-free survival with second-line treatment was 17 months. For the third line of therapy, lenvatinib and pembrolizumab were used in combination with bevacizumab. Currently, he has had stable disease for approximately 6 months during third-line treatment. CONCLUSION: Adding pyrotinib to pembrolizumab and lenvatinib may represent a promising strategy for advanced ICC patients who have high levels of HER2.

Atomically Dispersed Au-Assisted C-C Coupling on Red Phosphorus for CO2 Photoreduction to C2H6.

Single-atom catalysts have exhibited great potential in the photocatalytic conversion of CO2 to C2 products, but generation of gaseous multi-carbon hydrocarbon products is still challenging. Previously, supports of a single atom consist of multiple elements, making C-C coupling difficult because the coordination environment of single-atom sites is diversified and difficult to control. Here, we steer C-C coupling by implanting an Au single atom on the red phosphorus (Au1/RP), support with uniform structure composed of a single element, lower electronegativity, and better ability to absorb CO2. The electron-rich phosphorus atoms near the Au single atoms can function as active sites for CO2 activation. The Au single atom can effectively reduce the energy barrier of C-C coupling, boosting the reaction kinetics of the formation of C2H6. Notably, the C2H6 selectivity and turnover frequency of Au1/RP reach 96% and 7.39 h-1 without a sacrificial agent, respectively, which almost represents the best photocatalyst for C2 chemical synthesis to date. This research will provide new ideas for the design of high-efficiency photocatalysts for CO2 conversion to C2 products.

Automated tumor proportion scoring for PD-L1 expression based on multistage ensemble strategy in non-small cell lung cancer.

INTRODUCTION: Programmed cell death ligand-1 (PD-L1) expression is a promising biomarker for identifying treatment related to non-small cell lung cancer (NSCLC). Automated image analysis served as an aided PD-L1 scoring tool for pathologists to reduce inter- and intrareader variability. We developed a novel automated tumor proportion scoring (TPS) algorithm, and evaluated the concordance of this image analysis algorithm with pathologist scores. METHODS: We included 230 NSCLC samples prepared and stained using the PD-L1(SP263) and PD-L1(22C3) antibodies separately. The scoring algorithm was based on regional segmentation and cellular detection. We used 30 PD-L1(SP263) slides for algorithm training and validation. RESULTS: Overall, 192 SP263 samples and 117 22C3 samples were amenable to image analysis scoring. Automated image analysis and pathologist scores were highly concordant [intraclass correlation coefficient (ICC) = 0.873 and 0.737]. Concordances at moderate and high cutoff values were better than at low cutoff values significantly. For SP263 and 22C3, the concordances in squamous cell carcinomas were better than adenocarcinomas (SP263 ICC = 0.884 vs 0.783; 22C3 ICC = 0.782 vs 0.500). In addition, our automated immune cell proportion scoring (IPS) scores achieved high positive correlation with the pathologists TPS scores. CONCLUSIONS: The novel automated image analysis scoring algorithm permitted quantitative comparison with existing PD-L1 diagnostic assays and demonstrated effectiveness by combining cellular and regional information for image algorithm training. Meanwhile, the fact that concordances vary in different subtypes of NSCLC samples, which should be considered in algorithm development.

Combined blockade of TGf-ß1 and GM-CSF improves chemotherapeutic effects for pancreatic cancer by modulating tumor microenvironment.

The interactions between tumor immune microenvironment (TIME) and pancreatic cancer cells can affect chemotherapeutic efficacy; however, the mechanisms still remain largely unknown. Thirty items in TIME were comprehensively screened by using tissue microarray from pancreatic cancer patients. Their expressions, interconnections and predictive roles for survival were analyzed. Twenty-one of 30 items could stratify the survival of the patients; however, multivariate analysis found that only 5 independent risk factors could predict worse survival (M2-polarized tumor-associated macrophages (TAMs), IgG4 positive cells, TGF-ß1, GM-CSF and lymphangiogenesis). They had a much higher expression levels in tumoral tissue, compared to peritumoral tissue. The Spearman analysis showed that M2-polarized TAM, TGF-ß1 and GM-CSF were positively correlated with pancreatic cancer stem cells (PCSC), angiogenesis and lymphangiogenesis. Both human and murine pancreatic cancer cells could induce M2-polarized TAM, which showed substantial roles to decease chemotherapeutic effects. After treated by gemcitabine, both human and murine pancreatic cancer cell lines expressed higher level of immune check points, PCSC markers and varieties of immunosuppressive factors; however, TGF-ß1 and GM-CSF had the highest increase. Based on the above results, TGF-ß1 and GM-CSF were proposed to be the optimal potential targets to improve chemotherapeutic effects. In immunocompetent murine models, we demonstrated that combined blockade of TGF-ß1 and GM-CSF improved the chemotherapeutic effects by inhibition of M2-polarized TAM and induction of CD8 positive T cells. This study presents a novel promising combined strategy to improve the chemotherapeutic effects for pancreatic cancer.

An animal model of transfusion-related acute lung injury and the role of soluble CD40 ligand.

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is a life-threatening complication of transfusion and is one of leading causes of transfusion-associated fatalities. However, the pathogenesis of TRALI is still unclear. Soluble CD40 ligand (sCD40L) is a proinflammatory cytokine that accumulates during blood component storage and is involved in transfusion reactions. The objective of this study was to establish a clinically relevant TRALI animal model and to evaluate the role of sCD40L in TRALI. MATERIALS AND METHODS: Rats' red-blood-cell (RBC) suspensions were prepared, and the quality of RBC was evaluated. A trauma-haemorrhage-transfusion strategy was applied to build the animal model. Lung oedema was evaluated by histopathology examination, total bronchoalveolar lavage fluid (BALF) protein concentration, Evans blue dye (EBD) leakage and inflammatory cytokines. The sCD40L concentrations were measured. RESULTS: Storage lesions of RBCs gradually increased over time. Obvious histological evidence of lung injury of rats transfused with a 35-day RBC was observed. The total BALF protein concentration, EBD leakage, inflammatory cytokines concentration were increased significantly in the Day 35 group. The sCD40L concentration increased significantly in the storage RBC suspension over time but was slightly elevated in rat plasma. CONCLUSIONS: These findings indicated successful establishment of a TRALI animal model with trauma-haemorrhage-transfusion, in which sCD40L may play a minor role in the development of TRALI.

Peripheral T cell lymphoma after chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): a case report.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological characteristics. The pathophysiology of CLIPPERS still remains unclear. Because a few cases about lymphoma mimicking the manifestations of CLIPPERS were reported and the prognosis of lymphoma is much worse, early identification of lymphoma is very important. CASE PRESENTATION: A 31-year-old woman was admitted with 3 months' history of diplopia, dizziness, gait ataxia, and right facial numbness. The diagnosis of CLIPPERS was established based on the finding of punctate enhancing lesions in the cerebellum, thalamus, pons, medulla, and midbrain region in magnetic resonance imaging (MRI), together with the favorable clinical and radiological responses to corticosteroids. However, she was diagnosed as peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) by the pulmonary nodular and the skin biopsy almost 10 years later, and she got complete remission within 1 year after chemotherapy. CONCLUSION: We report the first case of CLIPPERS developing PTCL-NOS. This case proposes that when brain biopsy was difficult to achieve, biopsies in extra-cerebral lesions under the assisting examination of positron emission tomography-computed tomography (PET-CT) can be helpful in further identification.

Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice.

BACKGROUND/AIMS: Retinitis pigmentosa (RP) is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. METHODS: Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1) mice. RESULTS: The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. CONCLUSIONS: Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP.

Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection.

Interactions between pancreatic cancer cells and inflammatory cells play crucial roles in the biological behavior of pancreatic cancer. Abundant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in the pancreas is the most significant feature of autoimmune pancreatitis; however, the clinical significance of IgG4-positive plasma cell infiltration in pancreatic cancer has not previously been reported. Herein, we analyzed intratumoral and peritumoral infiltrations of IgG4-positive plasma cells in 95 pancreatic cancer cases after curative resection. The correlations between IgG4-positive plasma cell infiltration and the clinicopathologic traits and overall survival of pancreatic cancer were investigated. IgG4-positive plasma cells were found in 86 % of tumor tissue samples compared with 69 % of peritumoral tissue samples (P = 0.0063). The high-level infiltration of intratumoral IgG4-positive plasma cells was positively correlated with poor histological grade (P = 0.017). The high-level infiltration of intratumoral IgG4-positive plasma cells was significantly correlated with worse prognosis (P = 0.01) in multivariate analysis. We further found that intratumoral M2-polarized tumor-associated macrophages (TAMs) were positively, linearly correlated with IgG4-positive plasma cells. In conclusion, IgG4-positive plasma cell infiltration is correlated with the clinicopathologic traits and overall survival of pancreatic cancer. High-level intratumoral infiltration of IgG4-positive plasma cells is an independent predictor for poor overall survival in pancreatic cancer patients after curative resection. Intratumoral M2-polarized TAMs probably induce IgG4-positive plasma cells.

Cancer-associated fibroblasts in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most highly malignant tumors with a very poor prognosis. In addition to the cancer cells, the stroma of tumor can expand by 50% and influence cancer cell growth. Cancer-associated fibroblasts (CAFs) are important components of tumor stroma. Cancer cells, normal fibroblasts, normal epithelial cells as well as bone marrow-derived myofibroblasts contribute to the emergence of CAFs through various cytokines (e.g., TGF-ß, SHH, PDGF) and epithelial-to-mesenchymal transition. CAFs affect cancer growth, survival, metastasis, angiogenesis and immunosurveillance through the secretion of various cytokines, such as CXCL12 and secreted protein acidic and rich in cystein. Also, CAFs correlate to the prognosis and chemoresistance of PDAC patients. As novel therapeutic targets, CAFs, and their relative factors, represent an important role in PDAC therapy.

Clinical Characteristics of Adrenal Hemangioma.

Objective: Adrenal hemangioma (AH) is a rare, benign adrenal tumor often detected incidentally by imaging. This retrospective study aimed to investigate the clinical characteristics of AH, including clinical and diagnostic imaging features, to improve the recognition and understanding of AH. Methods: We retrospectively analyzed the medical records of patients diagnosed with AH at Peking Union Medical College Hospital between 2008 and 2022. Clinical manifestations, adrenal hormone levels, imaging findings, treatment approaches, and pathological results were collected and analyzed. Results: Of the 7140 adrenal tumor patients, 40 (0.56%) had AH confirmed postoperatively. The mean age at diagnosis was 53.9 years, with a female predominance. Most (70%) were asymptomatic and diagnosed incidentally. Misdiagnosis before surgery was common, most frequently as pheochromocytoma. Imaging characteristics, especially enhanced computed tomography, revealed distinct features based on tumor size. Surgery was the main treatment, with laparoscopic adrenalectomy preferred. Conclusion: This study elucidates the clinical characteristics of AH, including demographics, diagnostic challenges, and imaging features. AH often presents incidentally and is frequently misdiagnosed preoperatively. Recognizing distinct imaging characteristics and appropriate surgical management can enable accurate diagnosis and optimal treatment.

Can a nomogram predict apical prostate cancer pathology upgrade from fusion biopsy to final pathology? A multicenter study.

BACKGROUND: This study evaluates the efficacy of a nomogram for predicting the pathology upgrade of apical prostate cancer (PCa). METHODS: A total of 754 eligible patients were diagnosed with apical PCa through combined systematic and magnetic resonance imaging (MRI)-targeted prostate biopsy followed by radical prostatectomy (RP) were retrospectively identified from two hospitals (training: 754, internal validation: 182, internal-external validation: 148). A nomogram for the identification of apical tumors in high-risk pathology upgrades through comparing the results of biopsy and RP was established incorporating statistically significant risk factors based on univariable and multivariable logistic regression. The nomogram's performance was assessed via the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA). RESULTS: Univariable and multivariable analysis identified age, targeted biopsy, number of targeted cores, TNM stage, and the prostate imaging-reporting and data system score as significant predictors of apical tumor pathological progression. Our nomogram, based on these variables, demonstrated ROC curves for pathology upgrade with values of 0.883 (95% CI, 0.847-0.929), 0.865 (95% CI, 0.790-0.945), and 0.840 (95% CI, 0.742-0.904) for the training, internal validation and internal-external validation cohorts respectively. Calibration curves showed good consistency between the predicted and actual outcomes. The validation groups also showed great generalizability with the calibration curves. DCA results also demonstrated excellent performance for our nomogram with positive benefit across a threshold probability range of 0-0.9 for the training and internal validation group, and 0-0.6 for the internal-external validation group. CONCLUSION: The nomogram, integrating clinical, radiological, and pathological data, effectively predicts the risk of pathology upgrade in apical PCa tumors. It holds significant potential to guide clinicians in optimizing the surgical management of these patients.

PD-L1 expression in ovarian clear cell carcinoma using the 22C3 pharmDx assay.

BACKGROUND: Ovarian clear cell carcinoma (OCCC), well known for its chemoresistance to platinum-based chemotherapy, exhibited a good response in clinical trials of anti-PD-1/PD-L1 inhibitors. By assessing PD-L1 expression, we sought to determine the potential therapeutic benefit of PD-1/PD-L1 inhibitors in OCCC. METHODS AND RESULTS: The retrospective study included 152 individuals with OCCC between 2019 and 2022 at Peking Union Medical College Hospital. Paired tumors of primary versus recurrent lesions (17 pairs from 15 patients) or primary versus metastatic lesions (11 pairs from 9 patients) were also included. The 22C3 pharmDx assay and whole sections were used for PD-L1 immunohistochemical staining. Pathologists with experience in premarket clinical trials evaluated PD-L1 expression based on various diagnostic criteria (TPS 1%, CPS 1, or CPS 10). The number and percentage of positive PD-L1 cases were 34 (22.4%, TPS ≥ 1%) and 59 (38.8%, CPS ≥ 1), respectively. Thirty-three (21.7%) of the cases had high PD-L1 expression (CPS ≥ 10). Half of the platinum-resistant patients (11/22) were PD-L1 positive (CPS ≥ 1). In addition, positive PD-L1 expression (CPS ≥ 1) was related to clinicopathological characteristics that represented a worse prognosis, such as advanced stages, lymph node metastasis, and distant metastasis (p = 0.032, p < 0.001 and p = 0.003, separately). PD-L1 was expressed equally or more in the recurrent lesion compared with its matched primary lesion. CONCLUSIONS: In conclusion, anti-PD-1/PD-L1 inhibitors are a promising therapeutic choice for OCCC. For evaluation of PD-L1 expression, CPS is more recommended than TPS. Evaluation of recurrent lesion was still suitable and predictive when the primary tumor tissue was not available. Distant metastatic lesions can serve as alternative samples for PD-L1 evaluation, while usage of lymphatic metastatic lesions is not recommended.

Clinical spectrum of Chinese hospitalized lung cancer patients with concomitant interstitial lung disease: before and after the new era of LC treatment.

This study aimed to explore the general characteristics and spectrum of hospitalized Chinese patients suffering from lung cancer with concomitant interstitial lung disease (LC-ILD). Furthermore, we compared their features before and after the period of immunotherapy for lung cancer. A retrospective analysis of the clinical characteristics of hospitalized LC patients with definite pathological diagnoses was performed from 2014 to 2021. ILD was defined after the review of chest CT imaging. There were 13,085 hospitalized LC patients. Among them, 509 patients (3.89%) had 551 cases of ILD. There were variable underlying causes of ILD, including idiopathic interstitial pneumonia (360 patients), LC treatment-associated ILD (134 cases), and connective tissue disease-associated ILD (55 patients). Although most LC-ILD patients were suffering from adenocarcinoma (204/40.1%), SCLC patients were prone to concomitant ILD (10.8% of all SCLC cases), followed by SCC (9.6% of all SCC cases). All but 10 LC-ILD patients received anti-LC treatment; however, only 39 (10.8%) LC-IIP patients received anti-ILD treatment. There were more LC-ILD patients in the 2018-2021 group than in the 2014-2017 group (5.16% vs. 2.03%, p < 0.001). The underlying causes of ILD were significantly different between the 2018-2021 group and the 2014-2017 group (p < 0.001). After adjusting for the number of hospitalized patients having the same LC pathological pattern, SCLC was determined to be the most likely to be concomitant with ILD, followed by SCC. Most LC-ILD patients were scheduled for anti-LC therapy; however, treatments for concomitant IIP were usually ignored. LC treatment-associated ILD should receive more attention than before.

Malignancy-associated membranous nephropathy: focus on diagnosis and treatment.

BACKGROUND: The clinicopathological features of malignancy-associated membranous nephropathy have been described previously, but information about diagnosis and treatment remains limited. METHODS: Patients with malignancy-associated membranous nephropathy in a tertiary hospital in China between June 2012 and October 2021 were retrospectively reviewed. RESULTS: Forty-two patients with malignancy-associated membranous nephropathy were identified. Compared to patients with idiopathic membranous nephropathy, patients with malignancy-associated membranous nephropathy were older and less frequently showed glomerular phospholipase A2 receptor staining (37.9% vs 85.0%) and IgG4 predominant deposition (66.7% vs 95.0%). At diagnosis of membranous nephropathy, the malignancy was unknown in 67% (28/42) of patients and was detected only by tumor screening. Among the 19 patients with concurrent diagnosis of cancer and biopsy-proven membranous nephropathy, 15 received anticancer treatment alone initially. Six of the 10 patients who attained cancer remission achieved remission of membranous nephropathy, while none of the 5 patients without remission of cancer did, suggesting a causal relationship between the two diseases. Some patients with persistent or relapsing membranous nephropathy following cancer remission achieved remission of membranous nephropathy after immunosuppressive therapy. Over a median follow-up of 24 months, 25% (10/40) of patients died, mainly due to neoplasia. CONCLUSIONS: Tumor screening is important in patients with membranous nephropathy, especially in elderly patients and patients with negative phospholipase A2 receptor or non-IgG4 predominant deposition. Remission of membranous nephropathy can be observed following remission of cancer in some cases. Immunosuppressive therapy may be considered if membranous nephropathy does not remit after remission of cancer.

Free-Breathing StarVIBE Sequence for the Detection of Extranodal Extension in Head and Neck Cancer: An Image Quality and Diagnostic Performance Study.

(1) Background: This study aims to evaluate the image quality of abnormal cervical lymph nodes in head and neck cancer and the diagnostic performance of detecting extranodal extension (ENE) using free-breathing StarVIBE. (2) Methods: In this retrospective analysis, 80 consecutive head and neck cancer patients underwent StarVIBE before neck dissection at an academic center. Image quality was compared with conventional VIBE available for 28 of these patients. A total of 73 suspicious metastatic lymph nodes from 40 patients were found based on morphology and enhancement pattern on StarVIBE. Sensitivity (SN), specificity (SP), and odds ratios were calculated for each MR feature from StarVIBE to predict pathologic ENE. (3) Results: StarVIBE showed significantly superior image quality, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) for enlarged lymph nodes compared to VIBE. The MR findings of "invading adjacent planes" (SN, 0.54; SP, 1.00) and "matted nodes" (SN, 0.72; SP, 0.89) emerged as notable observations. The highest diagnostic performance was attained by combining these two features (SN, 0.93; SP, 0.89). (4) Conclusions: This study confirms that StarVIBE offers superior image quality for abnormal lymph nodes compared to VIBE, and it can accurately diagnose ENE by utilizing a composite MR criterion in head and neck cancer.

T1 and T2 mapping for identifying malignant lymph nodes in head and neck squamous cell carcinoma.

BACKGROUND: This study seeks to assess the utility of T1 and T2 mapping in distinguishing metastatic lymph nodes from reactive lymphadenopathy in patients with head and neck squamous cell carcinoma (HNSCC), using diffusion-weighted imaging (DWI) as a comparison. METHODS: Between July 2017 and November 2019, 46 HNSCC patients underwent neck MRI inclusive of T1 and T2 mapping and DWI. Quantitative measurements derived from preoperative T1 and T2 mapping and DWI of metastatic and non-metastatic lymph nodes were compared using independent samples t-test or Mann-Whitney U test. Receiver operating characteristic curves and the DeLong test were employed to determine the most effective diagnostic methodology. RESULTS: We examined a total of 122 lymph nodes, 45 (36.9%) of which were metastatic proven by pathology. Mean T2 values for metastatic lymph nodes were significantly lower than those for benign lymph nodes (p < 0.001). Conversely, metastatic lymph nodes exhibited significantly higher apparent diffusion coefficient (ADC) and standard deviation of T1 values (T1SD) (p < 0.001). T2 generated a significantly higher area under the curve (AUC) of 0.890 (0.826-0.954) compared to T1SD (0.711 [0.613-0.809]) and ADC (0.660 [0.562-0.758]) (p = 0.007 and p < 0.001). Combining T2, T1SD, ADC, and lymph node size achieved an AUC of 0.929 (0.875-0.983), which did not significantly enhance diagnostic performance over using T2 alone (p = 0.089). CONCLUSIONS: The application of T1 and T2 mapping is feasible in differentiating metastatic from non-metastatic lymph nodes in HNSCC and can improve diagnostic efficacy compared to DWI.

Diagnostic significance of parafibromin expression in parathyroid carcinoma.

Parathyroid carcinomas are difficult to distinguish from adenomas according to the current diagnostic criteria. The judgment of local infiltration is subjective and inconsistent. Existing studies have found that the CDC73 gene encoding parafibromin is related to the occurrence of parathyroid carcinomas. This study is aimed at investigating whether the immunohistochemistry of parafibromin is helpful in distinguishing malignant from benign parathyroid tumors. A total of 53 patients with parathyroid carcinoma from Peking Union Medical College Hospital were included. Metastasis was found in 17 of 53 patients. In addition, another 53 patients with parathyroid adenomas were included as controls. Appropriate sections were stained with an immunohistochemical autostainer. Three senior pathologists evaluated the sections and analyzed their clinicopathological features independently. The loss of parafibromin expression only occurred in malignant tumors, including all carcinomas with metastasis (17/17) and 14 of 36 carcinomas with only local infiltration. All staining results of adenomas (53/53) were positive. Considering invasion as the gold standard of malignancy, the sensitivity of parafibromin staining is 58%, and the specificity is 100%. If the gold standard is changed to metastasis, the sensitivity becomes 100%, and the specificity becomes 84%. By analyzing clinicopathological features with metastasis and parafibromin staining, it is found that local-infiltrative carcinomas with positive staining results have better biological behaviors than carcinomas that lack parafibromin expression. Parafibromin staining is highly recommended as an auxiliary method in the diagnosis of parathyroid carcinoma.

Phase 2 study of oral thalidomide-cyclophosphamide-dexamethasone for recurrent/refractory adult Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm with various clinical manifestations and heterogeneous prognoses. No standard therapy is available for recurrent/refractory LCH patients. This single-center, single-arm, phase 2 study enrolled 32 patients diagnosed with recurrent/refractory LCH. The TCD regimen (thalidomide 100 mg daily, cyclophosphamide 300 mg/m2 Day 1, 8, 15, and dexamethasone 40 mg Day 1, 8, 15, 22 every 4 weeks) was administered for 12 cycles and thalidomide alone as maintenance for 12 months. The primary endpoint was event-free survival (EFS). Events were defined as progression during or after TCD therapy or death from any cause. After a median follow-up of 22 months (range 5-24 months), no patient died of all causes. The overall response rate was 87.5%, including 18 patients (56.3%) achieving complete remission and 10 patients (31.3%) as partial remission. The estimated 24-month EFS was 64.0%. Patients with risk organ involvement had similar EFS compared to patients without risk organ involvement (P = 0.38). The common toxicities of TCD regimen include grade 1-2 neutropenia (18.8%), grade 1-2 constipation (12.5%), grade 1-2 tiredness (9.4%) and grade 2 peripheral neuropathy (12.5%). Oral thalidomide, cyclophosphamide and dexamethasone are effective and safe regimen for recurrent/refractory LCH patients, particularly for patients with risk organ involvement.