Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer / 中华医学杂志(英文版)

BACKGROUND@#Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.@*METHODS@#The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.@*RESULTS@#Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.@*CONCLUSIONS@#The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Comparative study of orthopaedic robot-assisted minimally invasive surgery and open surgery for limb osteoid osteoma / 中国修复重建外科杂志

OBJECTIVE@#To compare the accuracy and effectiveness of orthopaedic robot-assisted minimally invasive surgery versus open surgery for limb osteoid osteoma.@*METHODS@#A clinical data of 36 patients with limb osteoid osteomas admitted between June 2016 and June 2023 was retrospectively analyzed. Among them, 16 patients underwent orthopaedic robot-assisted minimally invasive surgery (robot-assisted surgery group), and 20 patients underwent tumor resection after lotcated by C-arm X-ray fluoroscopy (open surgery group). There was no significant difference between the two groups in the gender, age, lesion site, tumor nidus diameter, and preoperative pain visual analogue scale (VAS) scores ( P>0.05). The operation time, lesion resection time, intraoperative blood loss, intraoperative fluoroscopy frequency, lesion resection accuracy, and postoperative analgesic use frequency were recorded and compared between the two groups. The VAS scores for pain severity were compared preoperatively and at 3 days and 3 months postoperatively.@*RESULTS@#Compared with the open surgery group, the robot-assisted surgery group had a longer operation time, less intraoperative blood loss, less fluoroscopy frequency, less postoperative analgesic use frequency, and higher lesion resection accuracy ( P<0.05). There was no significant difference in lesion resection time ( P>0.05). All patients were followed up after surgery, with a follow-up period of 3-24 months (median, 12 months) in the two groups. No postoperative complication such as wound infection or fracture occurred in either group during follow-up. No tumor recurrence was observed during follow-up. The VAS scores significantly improved in both groups at 3 days and 3 months after surgery when compared with preoperative value ( P<0.05). The VAS score at 3 days after surgery was significantly lower in robot-assisted surgery group than that in open surgery group ( P<0.05). However, there was no significant difference in VAS scores at 3 months between the two groups ( P>0.05).@*CONCLUSION@#Compared with open surgery, robot-assisted resection of limb osteoid osteomas has longer operation time, but the accuracy of lesion resection improve, intraoperative blood loss reduce, and early postoperative pain is lighter. It has the advantages of precision and minimally invasive surgery.

Relation between Delay Time to Surgical Treatment of Prostate Cancer and Disease Recurrence Risk / Relação entre Tempo de Atraso no Tratamento Cirúrgico do Câncer de Próstata e Risco de Recorrência da Doença

De acordo com a literatura, não há consenso sobre um tempo de atraso razoável desde o diagnóstico até a operação da prostatectomia radical (PR) sem piora do prognóstico. Objetivo: Avaliar a influência desse tempo no risco de recorrência da doença em pacientes com adenocarcinoma acinar da próstata tratados com PR. Método: Quatrocentos e doze pacientes submetidos à PR foram avaliados retrospectivamente. Destes, 172 foram excluídos por dados incompletos e outros 28, por estadiamento pré- -operatório como câncer de próstata de alto risco (PSA > 10 ng/mL ou escore de Gleason na biópsia > 7). Os estadiamentos pré e pós-operatórios foram comparados, e a análise de sobrevida feita pelo método de Kaplan-Meier para examinar a influência do tempo na discordância entre os estadiamentos pré e pós-operatórios. Resultados: Para os 212 pacientes da amostra, o tempo médio desde o diagnóstico até a PR foi de 176,1 ± 120,2 dias (mediana de 145,5 dias), variando de 29 a um máximo de 798 dias. A curva de Kaplan-Meier indicou que o câncer piorava quanto maior o atraso entre o diagnóstico e a operação. Pacientes submetidos à cirurgia dentro de 60 dias tiveram cerca de 95% de probabilidade de não aumentarem o risco inicial de recorrência. Esse número caiu para 80%, 70% e 50% nos pacientes operados em até 100, 120 e 180 dias, respectivamente. Conclusão: O atraso na realização da PR representa risco contínuo de recorrência da neoplasia. O tempo ideal para PR é de até 60 dias a partir da biópsia da próstata, uma vez que a probabilidade de upstaging é inferior a 5% nesse período.

There is no consensus in the literature on a reasonable delay time from diagnosis to radical prostatectomy (RP) surgery, without worsening the prognosis. Objective: To evaluate the influence of the delay on the risk of disease recurrence in patients with acinar adenocarcinoma of the prostate treated with RP. Method: Four hundred and twelve patients undergoing RP were retrospectively evaluated. Of these, 172 were excluded due to incomplete data and another 28 due to preoperative staging as high-risk prostate cancer (PSA > 10 ng/mL or Gleason score on biopsy > 7). Pre-and postoperative stagings were compared and survival analysis was performed using the Kaplan-Meier method to investigate the influence of time on discordance between pre- and postoperative stagings. Results:For the 212 patients of the sample, the average time from diagnosis to RP was 176.1 ± 120.2 days (median 145.5 days), ranging from 29 to a maximum of 798 days. The Kaplan-Meier curve indicated that the cancer worsened the longer the delay between diagnosis and surgery. Patients undergoing surgery within 60 days had an approximately 95% probability of not increasing the initial risk of recurrence. This number fell to 80%, 70% and 50% in patients operated on up to 100, 120 and 180 days, respectively. Conclusion:Delay in performing RP represents a continuous risk of relapse. The ideal time for RP is up to 60 days from prostate biopsy, as the probability of upstaging is less than 5% in this period

Según la literatura, no existe consenso sobre un tiempo razonable de retraso desde el diagnóstico hasta la cirugía de prostatectomía radical (PR), sin empeorar el pronóstico. Objetivo: Evaluar la influencia de este tiempo sobre el riesgo de recurrencia de la enfermedad en pacientes con adenocarcinoma acinar de próstata tratados con PR. Método: Se evaluaron retrospectivamente 412 pacientes sometidos a PR. De ellos, 172 fueron excluidos por datos incompletos y otros 28 por estadificación preoperatoria como cáncer de próstata de alto riesgo (PSA > 10 ng/mL o puntuación de Gleason en la biopsia > 7). Se compararon las estadificaciones pre y posoperatorias y se realizó un análisis de supervivencia utilizando el método de Kaplan-Meier para examinar la influencia del tiempo en la discordancia entre las estadificaciones pre y posoperatorias. Resultados: Para los 212 pacientes de la muestra, el tiempo promedio desde el diagnóstico hasta la PR fue de 176,1 ± 120,2 días (mediana 145,5 días), oscilando entre 29 y 798 días. La curva de Kaplan-Meier indicó que el cáncer empeoraba cuanto mayor era el retraso entre el diagnóstico y la cirugía. Los pacientes sometidos a cirugía dentro de los 60 días tenían aproximadamente un 95% de probabilidad de no aumentar el riesgo inicial de recurrencia. Esta cifra cayó al 80%, 70% y 50% en los pacientes operados hasta 100, 120 y 180 días, respectivamente. Conclusión: El retraso en la realización de la PR representa un riesgo continuo de restablecimiento de la neoplasia. El momento ideal para la PR es hasta los 60 días desde la biopsia de próstata, ya que la probabilidad de upstaging es inferior al 5% en este periodo.

Prognostic roles and survival benefits of endoscopic resection versus surgical resection in the management of malignant colon polyps

Background: Due to few sufficient data regarding the comparison between endoscopic and surgical resection of malignant colorectal polyps regarding outcomes and survival benefits, there are no clear guidelines of management strategies of malignant colorectal polyps. The aims of the present study were to compare endoscopic resection alone and surgical resection in patients with malignant polyps in the colon (T1N0M0) readings advantages, disadvantages, recurrence risks, survival benefits, and long-term prognosis to detect how management strategy affects outcome. Patients and methods: we included 350 patients. All included patients were divided into 2 groups; the first group included 100 patients who underwent only endoscopic polypectomy and the second group included 250 patients who underwent endoscopic polypectomy followed by definitive surgical resection after histopathological diagnosis. We followed all patients for about 5 years, ranging from 18 to 55 months. The primarily evaluated parameters are surgical consequences and patients' morbidity. The secondary evaluated parameters are recurrence risks, recurrence free survival, and overall survival rates. Results: The age of patients who underwent polypectomy is usually younger than the surgical group, males have more liability to polypectomy in comparison with females. Patients with tumors in the left colon have more liability to polypectomy in comparison with the right colon (p< 0.0001). Tumor factors associated with more liability to surgical resection are presence of lymphovascular invasion, high grade, and poor tumor differentiation (p< 0.0001). The management strategy was the most significant predictor of overall and recurrence free survival rates in patients with malignant colon polyps (p< 0.001). Conclusions: We found that survival benefits and lower incidence of recurrence are detected in the surgical resection group more than in the polypectomy group. (AU)

Use of artificial intelligence to predict response to neoadjuvant chemotherapy in breast cancer

:Breast cancer is the object of thousands of studies worldwide. Nevertheless, few tools are available to corroborate prediction of response to neoadjuvant chemotherapy. Artificial intelligence is being researched for its potential utility in several fields of knowledge, including oncology. The development of a standardized Artificial intelligence-based predictive model for patients with breast cancer may help make clinical management more personalized and effective. We aimed to apply Artificial intelligence models to predict the response to neoadjuvant chemotherapy based solely on clinical and pathological data. Methods: Medical records of 130 patients treated with neoadjuvant chemotherapy were reviewed and divided into two groups: 90 samples to train the network and 40 samples to perform prospective testingand validate the results obtained by the Artificial intelligence method. Results: Using clinicopathologic data alone, the artificial neural network was able to correctly predict pathologic complete response in 83.3% of the cases. It also correctly predicted 95.6% of locoregional recurrence, as well as correctly determined whether patients were alive or dead at a given time point in 90% of the time. To date, no published research has used clinicopathologic data to predict the response to neoadjuvant chemotherapy in patients with breast cancer, thus highlighting the importance of the present study. Conclusions: Artificial neural network may become an interesting tool for predicting response to neoadjuvant chemotherapy, locoregional recurrence, systemic disease progression, and survival in patients with breast cancer (AU)

Clinical analysis of 5 adult laryngeal rhabdomyosarcoma / 临床耳鼻咽喉头颈外科杂志

Objective:To explore the clinical manifestations,the type of pathology, treatment and prognosis of laryngeal rhabdomyosarcoma, and to enhance the understanding of the clinical characteristics of the disease, while improving the diagnosis rateand reducing the misdiagnosis rate, in order to explore effective diagnosis and treatment methods. Methods:A retrospective analysis was conducted on the clinical data of 5 cases of laryngeal rhabdomyosarcoma treated in the First Affiliated Hospital of Zhengzhou University from May 2015 to May 2021. Results:All 5 cases of laryngeal rhabdomyosarcoma were misdiagnosed in the early stage. with tumors mostly occurring in the vocal cords and appearing as smooth mass. The clinical symptoms were mostly hoarseness. According to pathological classification, three cases were embryonic type, one case was polymorphic type, and one case was spindle type.Three patients died due to tumor recurrence, one patient had multiple systemic metastases, and another patient who underwent surgical resection in the early stage and supplemented with postoperative radiotherapy and chemotherapyhas been followed up to date without recurrence. Conclusion:Laryngeal rhabdomyosarcoma has low incidence rate, high malignancy degree and poor prognosis. It is easy to be misdiagnosed as a benign mass. Extensive surgical resection combined with radiotherapy and chemotherapy should be performed as soon as possible after diagnosis.

Piriform sinus hamartoma in children: a case report and literature review / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the clinical manifestations and treatment of laryngopharynx hamartoma in children. Methods:The clinical data of a child with piriform sinus hamartoma treated in our hospital were analyzed retrospectively. The age, gender, clinical manifestations, auxiliary examination, location of the tumor and surgical methods were analyzed. Results:The patient had a good prognosis after surgery, and no tumor recurrence was found after 1 year of follow-up. Conclusion:Laryngopharynx hamartoma is rare in children. It should be considered in children with laryngeal dysfunction and upper airway obstruction. Complete resection of the tumor is the key to postoperative recurrence.

Misdiagnosis of adenoid cystic carcinoma of oropharynx: a case report / 临床耳鼻咽喉头颈外科杂志

Adenoid cystic carcinoma usually occurs in the salivary glands of the head and neck. It is a malignant tumor with a high degree of malignancy, resistance to radiotherapy and chemotherapy and poor prognosis. The clinical course of adenoid cystic carcinoma is slow and easy to be misdiagnosed. The main diagnosis and treatment means are individualized and precise treatment under the multi-disciplinary consultation mode, that is, surgical treatment and radiotherapy and chemotherapy. Adenoid cystic carcinoma is prone to relapse and hematologic metastasis, and the traditional radiotherapy and chemotherapy based therapies have not achieved satisfactory efficacy in the past three decades. How to detect, diagnose and treat early is an urgent task faced by clinicians.

Tislelizumab monotherapy for the treatment of recurrent/metastatic head and neck squamous cell carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:The aim of this retrospective study is to evaluate the safety and efficacy of tislelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Methods:Six patients with recurrent/metastatic head and neck squamous cell carcinoma who received tislelizumab monotherapy in our hospital from 2018 to 2020 were retrospectively analyzed. The information of sex, age, TNM stage, efficacy, and adverse reactions were collected. All patients were recruited from the RATIONALE 102 study. The primary end point was the objective response rate, and other end points included progression-free survival and overall survival. We performed tumor immune-related gene sequencing and transcriptome sequencing analysis on the tumor tissues of the patient, and used bioinformatics methods to enrich immune cells and analyze signaling pathways. All analyses were performed using R 4.1. 0 software, SPSS Statistics 24.0 software and GraphPad Prism 8. Results:As of May 31, 2020, the median follow-up time was 26.35 months. The objective response rate with tislelizumab was 50.0%, the median progression-free survival was 6.44 months, and the estimated median survival was 20.07 months. The incidence of grade 3 or higher adverse reactions was 66.7%, including hyponatremia, hypokalemia, hypercalcemia, etc. The expression of macrophage, Treg and neutrophil-related genes are higher in immune-sensitive patients, and the signaling pathways of the intestinal immune network for IgA production, graft versus host disease and autoimmune thyroid disease are significantly activated. Conclusion:Tislelizumab was found to be controllable and tolerable in patients with recurrent/metastatic head and neck squamous cell carcinoma. The response to tislelizumab is related to immune cell infiltration and activation of immune-related signaling pathways.

A case of sinonasal inverted papilloma with malignant transformation and distant metastasis: a 10-year follow-up report / 临床耳鼻咽喉头颈外科杂志

Sinonasal inverted papilloma（SNIP） is a kind of benign tumor originating from the nasal cavity and paranasal sinuses, accounting for 70% of papillomas. The incidence of the disease is more common in males, with an average age of 50-60 years. It is most likely to occur in unilateral maxillary sinus and ethmoid sinus, followed by sphenoid sinus and frontal sinus.It has the characteristics of local invasion, high recurrence rate and malignant tendency, and most malignant transformation into squamous cell carcinoma. Endoscopic nasal resection and appropriate adjuvant therapy can help to reduce the recurrence rate and inhibit further deterioration. We report the results of a 10-year follow-up of a SNIP patient, including the clinical manifestations, recurrence course and treatment plan during the 10 years. The patient underwent multiple nasal endoscopic surgeries, and had a recurrence of multiple focal attachment pattern, and finally had direct invasion and distant metastasis. Tumor recurrence and further deterioration persisted despite the use of a comprehensive treatment.

Composite B-cell and T-cell lymphomas: clinical, pathological, and molecular features of three cases and literature review / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.

Effect of Calcification on the Ultrasound-Guided Radiofrequency Ablation of Papillary Thyroid Carcinoma / 中国医学科学院学报

Objective To investigate the effect of calcification on the ultrasound-guided radiofrequency ablation(RFA)of papillary thyroid carcinoma(PTC).Methods We retrospectively analyzed the preoperative and follow-up data of 164 patients(182 nodules)with PTC treated by percutaneous ultrasound-guided RFA in the First Medical Center of Chinese PLA General Hospital from January 1,2018 to December 31,2021.The tumor status 12 months after RFA was taken as the endpoint event.The univariate Logistic regression analysis was employed to predict the influencing factors of incomplete ablation.The factors were then included in the multivariate Logistic regression analysis for prediction of the independent risk factors of incomplete ablation.Results The maximum nodule diameter(OR=1.16,95%CI=1.04-1.29,P=0.009)and calcification ratio >2/3(OR=19.27,95%CI=4.02-92.28,P<0.001)were the factors influencing the disappearance of lesion 12 months after RFA.Conclusions PTC with calcification can be treated with ultrasound-guided RFA.In the case of calcification ratio ≤ 2/3,this therapy demonstrates the effect equivalent to that of no calcification.

Glutamine synthetase-negative hepatocellular carcinoma has better prognosis and response to sorafenib treatment after hepatectomy / 中华医学杂志(英文版)

BACKGROUND@#Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear.@*METHODS@#We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted.@*RESULTS@#Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways.@*CONCLUSIONS@#GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.

Clinical Analysis of Autologous Peripheral Blood Hematopoietic Stem Cells Mobilization and Collection in Lymphoma Patients / 中国实验血液学杂志

OBJECTIVE@#To analyze the factors influencing collection of autologous peripheral blood hematopoietic stem cells in lymphoma patients.@*METHODS@#Clinical data of 74 patients who received autologous peripheral blood hematopoietic stem cells mobilization and collection in the 940th Hospital of Joint Logistic Support Force of PLA from April 2009 to April 2021 were collected. The effects of gender, age, disease type, stage, course of disease, chemotherapy cycle number, relapse, radiotherapy, disease status and blood routine indexes on the day of collection on peripheral blood hematopoietic stem cell collection were analyzed.@*RESULTS@#The success rate of collection was 95.9%(71/74), and the excellent rate of collection was 71.6%(53/74). There was a significantly statistical differentce in the number of CD34+ cells in grafts collected from patients with chemotherapy cycle ≤6 and >6 ［(9.1±5.2)×106/kg vs (6.4±3.7)×106/kg, P=0.031］. The number of CD34+ cells in the first collection was positively correlated with WBC count, hemoglobin, platelet count, neutrophil count, lymphocyte count, monocyte count and hematocrit value on the day of collection ( r value was 0.424,0.486,0.306,0.289,0.353,0.428,0.528, respectively). WBC count, hemoglobin, monocyte count and hematocrit value have higher predictive value for the first collection of CD34+ cells. The area under the receiver operating characteristic was 0.7061,0.7845,0.7319,0.7848, respectively.@*CONCLUSION@#Low dose CTX and VP16 chemotherapy combined with G-CSF can effectively mobilize autologous peripheral blood stem cells. The cycle number of chemotherapy relates to the collection of autologous peripheral blood stem cells. After mobilization, the success of the first collection can be better predicted by the blood routine indexes.

A case of pancreatic cancer treated with chemotherapy combined with immunotherapy and targeted therapy / 浙江大学学报·医学版

A 68-year-old male was admitted due to fatigue and poor appetite and diagnosed pathologically as pancreatic adenocarcinoma with liver metastasis. The tumor marker carbohydrate antigen 199 (CA199) level was 2003.4 U/mL. The patient received two cycles of modified FOLFIRINOX plus immune checkpoint inhibitor (penpulimab). However, the tumor did not shrink and CA199 level was even higher. Anlotinib was added from the 3rd cycle, and the size of primary tumor and metastatic lesions were significantly reduced. Laparoscopic distal pancreatectomy and splenectomy as well as liver metastasis resection was performed. Three cycles of combined therapy were adopted after surgery followed by maintenance therapy with anlotinib plus penpulimab. There was no evidence of tumor recurrence during the follow-up (nearly 19 months since diagnosis).

Research progress on circulating tumor DNA as a biomarker for minimal residual disease in solid tumors / 中国当代儿科杂志

Circulating tumor DNA (ctDNA) is emerging as a novel biomarker for tumor evaluation, offering advantages such as high sensitivity and specificity, minimal invasiveness, and absence of radiation. Currently, various techniques including gene sequencing and PCR are employed for ctDNA detection. The utilization of ctDNA for monitoring minimal residual disease (MRD) enables comprehensive assessment of tumor status and early identification of tumor recurrence, achieving a remarkable detection sensitivity of 0.01%. Therefore, ctDNA holds promise as a biomarker for early diagnosis, treatment response monitoring, and prognosis prediction in solid tumors. This article reviews the commonly used methods for detecting ctDNA and their advantages in evaluating tumor MRD and guiding clinical diagnosis and treatment.

Differential diagnosis and surgical management in chondrosarcoma of the jugular foramen / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.

Application of supraclavicular fasciocutaneous island flap for reconstruction after removal of tumors in parotid and auricle area / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the efficacy of supraclavicular fasciocutaneous island flap (SIF) for repairing the defect of parotid or auricle regions after tumor resection. Methods: From February 2019 to June 2021, 12 patients (11 males and 1 female, aged 54-77 years old), of whom 4 with parotid adenoid cystic carcinoma and 8 with auricular basal cell carcinoma underwent reconstruction surgery for postoperative defects in the parotid gland area and auricular area with SIF in the Department of Otorhinolaryngology Head and Neck Surgery, the Second Xiangya Hospital of Central South University and their clinical data were retrospectively analyzed. Size of the SIF, time for harvesting SIF, neck lymph node dissection and postoperative complications were recorded. Results: The flap areas were (6-9) cm × (8-13) cm, and the harvesting time for SIF ranged from 40 to 80 min, averaging 51.7 min. The donor sites were directly closed. All patients underwent ipsilateral levels Ⅰ-Ⅲ neck dissection, with 4 cases undergoing additional level Ⅳ neck dissection and 2 cases undergoing level Ⅳ-Ⅴ neck dissection. Of the 12 SIF, 10 were completely survival and 2 had flap arterial crisis with partial flap necrosis, in addition, 1 had donor site wound dehiscence. With follow-up of 10-42 months, there were no tumor recurrences in 10 patients, 1 patient was lost to follow-up at 10 months postoperatively, and 1 patient experienced local tumor recurrence at 11 months after surgery and died 15 months later. Conclusion: SIF is an easily harvested flap with good skin features matching the skin in parotid and auricle regions and less damage to donor site, and this flap has no need for microvascular anastomosis technique. SIF is feasible and effective for repairing defects in parotid and auricle area.

Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment / 北京大学学报(医学版)

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.