Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

Electroacupuncture Ameliorates Depression-Like Behaviors Comorbid to Chronic Neuropathic Pain via Tet1-Mediated Restoration of Adult Neurogenesis.

Although electroacupuncture (EA) stimulation is a widely used therapy for chronic pain and comorbid psychiatric disorders, its long-term effects on chronic neuropathic pain-induced depression and the underlying mechanisms remain elusive. In the present study, we found that EA stimulation was able to restore adult neurogenesis in the ventral dentate gyrus (DG), by both increasing neuronal differentiation and restoring the normal morphology of newborn dendrites, in mice with spared nerve injury surgery. By ablating the Nestin+ neural stem cells (NSCs) via diphtheria toxin fragment A expression, we further proved that neurogenesis in the ventral DG was crucial to the long-term, but not the immediate antidepressant effect of EA, nor was it associated with nociception. Furthermore, we found that the restoration of neurogenesis was dependent on Tet1-mediated epigenetic modification upon EA treatment. Tet1 could bind to the promoter of the Prox1 gene, thus catalyzing its demethylation and facilitating its expression, which finally contributed to the restoration of neurogenesis and amelioration of depression-like behaviors induced by chronic neuropathic pain. Thus, we conclude that EA stimulation restores inhibited Tet1 expression in hippocampal NSCs of mice with chronic neuropathic pain, and increased Tet1 expression ameliorates hypermethylation of Prox1 and restores normal adult neurogenesis in the ventral DG, which contributes to the long-term antidepressant effect of EA.

Diagnosis of mediastinal cysts: the role and safety of EUS-FNA with 19-gauge needle: a retrospective cohort study.

Background: Mediastinal cysts are uncommon, and their diagnosis remains a clinical challenge, especially for patients with a solid mass on computed tomography (CT). Endoscopic ultrasound (EUS) is considered a valuable method to differentiate mediastinal cysts and EUS-fine needle aspiration (FNA) is a strategy for obtaining specimens from the cysts for cytological diagnosis. This study aims to evaluate the safety and utility of EUS-FNA for diagnosis of mediastinal cysts. Methods: This was a retrospective analysis of patients who underwent EUS-FNA with 19-gauge needle at Tianjin Medical University Cancer Institute and Hospital and were further diagnosed with mediastinal cysts confirmed by cytological and surgical pathological results between January 2016 and December 2020. Safety was estimated by the incidence of reported adverse events (AEs). Patients were followed for 48 hours and 1 week after the EUS-FNA procedure to evaluate AEs. Results: A total of 20 patients were diagnosed with mediastinal cysts using EUS-FNA, yet only 5 were diagnosed by CT. There were 15 patients diagnosed with bronchogenic cyst, 4 with enteric cyst, and 1 with pericardial cyst. The EUS appearance of cyst content varied, ranging from anechoic (4 cases) to hypoechoic (16 cases). AEs occurred in 2/20 (10%) patients after the EUS-FNA indicating an acceptable low rate of AEs. For all anechoic cysts that underwent complete FNA drainage, 3 patients had good prognosis, whereas 1 experienced recurrence. For 16 patients with hypoechoic cysts, adequate tissue was obtained for cytological examination. No patient developed an infection-related complication. Conclusions: For the diagnosis of mediastinal cysts, EUS-FNA was more accurate than CT. The EUS-FNA of mediastinal cysts is safe with an acceptable low rate of AEs when antibiotic prophylaxis is used postoperatively. Cysts containing free-flowing fluid can be achieved with complete needle drainage by a single pass with a 19-gauge needle.

Endoscopic ultrasound-guided fine needle aspiration for smooth benign appearing malignant esophageal stricture: a cross-sectional study.

Background: Endoscopic biopsy is standard for the diagnosis of esophageal malignancy. However, few cases are difficult to diagnose as they present with smooth esophageal stricture with negative biopsy results. We aimed to evaluate the effectiveness and safety of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of biopsy-negative suspected malignant esophageal strictures. Methods: We retrospectively analyzed cases of esophageal stricture with negative biopsies. From September 2016 to November 2021, 50 patients were enrolled. All the patients accepted the EUS-FNA examination. And histological and cytological specimens were obtained from all patients. Clinical, endoscopic, imaging, cytological, and histopathological results were noted and analyzed. Results: A total of 50 patients (40 male and 10 female) were enrolled in this study. The 19G puncture needle was used in 6 cases and the 22G puncture needle was used in 44 cases; an average of 2.7 needles were used per case. Satisfactory specimens were obtained by EUS-FNA for all subjects. All patients were diagnosed as malignant tumor. The diagnosis was confirmed by EUS-FNA biopsies in 98% of patients. Based on the surgical pathology results, there were 16 cases of esophageal squamous cell carcinoma, 2 cases of esophageal metastatic carcinoma, 1 case of esophageal sarcoma, 22 cases of lung cancer, 6 cases of mediastinal lymph node metastasis, and 3 cases of mediastinal tumor. No obvious complications were observed. A total of 5 cases were treated with surgery, 28 with chemotherapy, 3 with chemotherapy + surgery, and 12 with radiotherapy; 2 patients ceased treatment. No obvious complications, such as bleeding and mediastinal infection, were observed. Conclusions: EUS-FNA is effective and safe for the diagnosis of malignant esophageal strictures with smooth overlying esophageal mucosa. EUS-FNA is effective and safe for patients with smooth esophagus stenosis for whom satisfactory cytological and histological specimens can be obtained, and the diagnosis can be confirmed by cytological, histological, and immunohistochemical examinations. It can be used as the first choice for diagnosis and treatment.

A study on the efficacy of microwave ablation for benign thyroid nodules and related influencing factors.

OBJECTIVES: To explore the efficacy of microwave ablation (MWA) in the treatment of benign thyroid nodules, and analyze related influencing factors. METHODS: The clinical and ultrasound data of 115 patients with 115 benign thyroid nodules treated with MWA were retrospectively analyzed. The volume of nodules at 1, 3, 6, and 12 months after the procedure was obtained, and the volume reduction rate (VRR) at each time point was calculated. With VRR > 90% as the criterion for nodule cure, binary logistic regression was employed to screen the factors that affect the efficacy. RESULTS: ① At 1, 3, 6, and 12 months after the procedure, the volume of nodules continued to decrease, the VRR gradually increased, and the differences at each time point were statistically significant (p < 0.05). A total of 29 (25.21%) nodules disappeared completely at 12 months after the procedure; ② Multivariate stepwise logistic regression showed that there was a statistically significant difference for the internal component of nodules, enhancement mode, and immediate volume after the procedure in determining the ablation efficacy (p < 0.05); ③ The ROC curve was plotted for predicting the efficacy of MWA, with the results showing that the AUC, sensitivity, specificity, and accuracy were 0.82, 67.50, 88.00, 79.10%, respectively; ④ 11 cases (9.56%) had side effects, 10 cases (8.70%) had minor complications, and three cases (2.61%) had major complications. CONCLUSION: MWA is safe and effective in the treatment of benign thyroid nodules. The internal component of nodules, enhancement mode, and immediate volume after the procedure are independent factors that affect the efficacy of ablation.

Different Photosynthetic Responses of Pyropia yezoensis to Ultraviolet Radiation Under Changing Temperature and Photosynthetic Active Radiation Regimes.

Macroalgae play a crucial role in coastal marine ecosystems, but they are also subject to multiple challenges due to tidal and seasonal alterations. In this work, we investigated the photosynthetic response of Pyropia yezoensis to ultraviolet radiation (PAR: 400-700 nm; PAB: 280-700 nm) under changing temperatures (5, 10 and 15°C) and light intensities (200, 500 and 800 µmol photons m-2  s-1 ). Under low light intensity (200 µmol photons m-2  s-1 ), P. yezoensis showed the lowest sensitivity to ultraviolet radiation, regardless of temperature. However, higher temperatures inhibited the repair rates (r) and damage rates (k) of photosystem II (PSII) in P. yezoensis. However, under higher light intensities (500 and 800 µmol photons m-2  s-1 ), P. yezoensis showed higher sensitivity to UV radiation. Both r and the ratio of repair rate to damage rate (r:k) were significantly inhibited in P. yezoensis by PAB, regardless of temperature. In addition, higher temperatures significantly decreased the relative UV-inhibition rates, while an increased carbon fixation rate was found. Our study suggested that higher light intensities enhanced the sensitivity to UV radiation, while higher temperatures could relieve the stress caused by high light intensity and UV radiation.

Occurrence of lymphoma in non-gonadal organ during pregnancy: a report on four cases and literature review.

Lymphoma rarely occurs during pregnancy, making this condition difficult to define. Lymphomas that occur in reproductive organs during pregnancy exhibit unique clinical characteristics. Among the limited cases, non-Hodgkin's lymphoma (NHL) shows a considerably higher incidence rate than Hodgkin's lymphoma (HL); NHL also displays clinical characteristics, such as high aggressiveness, advanced stage, and poor outcome. This study reports on four cases of lymphomas in non-gonadal organs (HL, n=2; NHL, n=2) during pregnancy. The tumors rapidly progressed in all patients during pregnancy but remitted at the end of pregnancy and/or therapy. The two HL cases were nodular sclerosis classical HL and treated with chemotherapy after terminating the pregnancy. One of the NHL cases was primary cutaneous follicular center lymphoma, a B cell-derived indolent lymphoma. The patient was followed up without any therapy after terminating her pregnancy. The other case was a follicular lymphoma grade 3B, which was treated with chemotherapy after delivery. We also conducted a literature review of 165 lymphoma cases occurring during pregnancy reported from 1976 to 2013 to reveal the correlation between pregnancy and lymphoma progression. Immunohistochemistry studies were performed to determine the expression of estrogen/progesterone receptors (ER/PR), and ER was weakly positive and sporadic. We concluded that lymphomas occurring during pregnancy should be managed with a prompt and reasonable treatment. High estrogen level in maternal body may affect lymphoma progression.

[Analysis of Clinicopathological Characteristics and Prognosis of 112 Patients with Primary Waldeyer's Ring Lymphoma].

OBJECTIVE: To investigate the clinical and pathological characteristics of patients with primary Waldeyer's ring lymphomas (PWRL), and to analyze its therapeutic efficacy and prognostic factors. METHODS: A total of 112 patients with PWRL confirmed by pathological and immunohistochemical methods between January 2009 and January 2014 were studied. Clinical data were collected and analyzed retrospectively. RESULTS: PWRL accounted for 3.9% of lymphoma over the same period. Median age of patients with PWRL was 51.5 years old. The affected areas were tonsil, nasopharynx, tongue base and oropharynx, which accounted for 63.4% (71/112), 22.3% (25/112), 5.3% (6/112) and 4.5% (5/112) respectively. The most common pathological types of these four areas were diffused large B-cell lymphoma (DLBCL) and extranodal NK/T cell lymphoma (NKTCL) which accounted for 58% and 15.2%. The overall response rate (CR/CRu = 51.4%; PR = 30.8%) in all patients was 82.2%, the estimated 5-year overall survival (OS) rate were 71.6%. The 5-year OS rate were 94.7% in the group used Rituximab. Meanwhile, chemotherapy combined with radiotherapy could improve the outcome of T-cell PWRL patients and the 5-year OS rate were 88.9%. Age, disease stages, pathological types, IPI scores, LDH level, ß2-MG level and the efficacy of initial therapy were prognostic factors with statistical significance. Cox multivariate analysis showed that age of more than 60 years, LDH level, pathological types and the efficacy of the initial therapy were independently associated with OS. CONCLUSION: PWRL has a relatively good prognosis. The pathological types affect the prognosis directly and guide treatment. Combined modality therapy should be chosen for patients with PWRL. Patients with T-cell PWRL should accept chemotherapy combined with radiotherapy, while rituximab may be better for B-cell PWRL. The efficacy of initial therapy is crucial for the outcome of patients. Age and LDH level are also important prognostic factors.

[Significance of BIOMED-2 standardized IG/TCR gene rearrangement detection in paraffin-embedded section in lymphoma diagnosis].

OBJECTIVE: To explore the feasibility of detecting lymphoma with the application of BIOMED-2 standardized immunoglobulin/T cell receptor (IG/TCR) gene rearrangement system in formalin fixed paraffin-embedded (FFPE) tissue samples, and to discuss the relationship between the longest amplification fragment of extracted DNA and positive detection rate of different IGH V-J primers. METHODS: DNA was extracted from 50 cases of FFPE tissue samples. Multiplex-PCR amplifications were performed and then the IG/TCR gene rearrangements were analyzed using BIOMED-2 standardized clonality analysis system. RESULTS: (1)When the DNA concentration was diluted to 50-100 ng/µl from 100-500 ng/µl, the proportion of the longest amplification fragment (300-400 bp) of DNA was improved from 10.0% to 90.0% in 30 cases of diffuse large B cell lymphoma (DLBCL) wax roll samples (P<0.01). The positive rate of IGH+IGK was increased from 46.7% to 83.3%, the difference was statistically significant (P=0.006). The lengths of the longest amplification fragments of DNA were all longer than 300 bp in the paraffin section samples of DLBCL. The positive rate of IGH+IGK of these samples was 96.7%. The difference of the positive rate of IGH+IGK between the wax roll samples and the paraffin section samples had no statistical significance (P=0.195). (2)When the concentration of DNA was high, most of the longest amplification fragments of extracted DNA were 100 bp or 200 bp, and the detection rate of short fragment IGH FR3 was more stable than that of long fragment IGH FR1. (3)The clonality analysis of TCRG+TCRB in all 13 cases of peripheral T cell lymphoma samples showed positive results, while no positive IG/TCR clones were found in 7 cases of reactive lymphoid tissue hyperplasia in control group. CONCLUSION: Dilution of DNA is the only method to improve not only the proportion of longest fragment amplification but also the detection rate of clonality. The detection rate of IGH FR3 would not be affected by the concentration of DNA. The application of BIOMED-2 standardized IG/TCR gene rearrangement system in FFPE tissue samples plays an important role in the lymphoma diagnosis.

EBV associated lymphomas in 2008 WHO classification.

Epstein-Barr virus (EBV) is a ubiquitous γ-herpes virus that asymptomatically infects more than 90% of the world's population. The exact mechanism of EBV in oncogenesis is an area of active debate. However, EBV has been implicated in the pathogenesis of several kinds of lymphomas and lymphoproliferative disorders, including B-, T- and NK-cell derived. Subsequent studies have proven that the EBV gene expression product plays an activating and/or promoting role on lymphomagenesis, and paves the way for novel cellular therapies of EBV-associated lymphomas. This review concentrates on the pathology, morphology, treatment and prognosis of EBV-associated lymphomas in the 2008 WHO classification of tumors of hematopoietic and lymphoma tissues.