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2023  Vol. 50  No. 4

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Expert Forum
Progress on Multi-disciplinary Combined Therapy for Locally Advanced Hypopharyngeal Carcinoma
Abstract:

Given the important position and function of the hypopharynx, the preservation of organ function and survival improvement are equally important. The optimal role of multi-disciplinary combined treatment modality becoming increasingly important. The optimal laryngeal preservation strategy for hypopharyngeal cancer is under continuous exploration. With the constant research of surgery, radiotherapy, chemotherapy, and molecular targeted therapy, new laryngeal preservation strategies continue to emerge. Herein, we primarily summarize the advances in multi-disciplinary combined treatment and the future direction in the treatment of hypopharyngeal carcinoma.

Application of Laparoscopic Surgery in Ileostomy Reversal
Abstract:

In colorectal cancer surgery, loop ileostomy is sometimes necessary to prevent anastomotic leakage. Although ileostomy reversal is relatively simple, postoperative complication is inevitable. In recent years, laparoscopic surgery has been gradually applied in ileostomy reversal due to its small trauma, fast recovery, and low complications, exhibiting satisfactory short-term outcomes. This review analyzes the application of the laparoscopic technique in ileostomy surgery and explores the potential of total laparoscopic surgery, aiming to provide a new perspective for the clinical application of laparoscopic ileostomy reversal.

Frontier and Future of Immunotherapy for Pancreatic Cancer
Abstract:

Pancreatic cancer remains as one of the most lethal malignancies. Resistance to conventional therapies has led to little improvement in the survival of pancreatic cancer patients over the past few decades. Immune-based treatment strategies for pancreatic cancer, such as immune-checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies show promise. Many immunotherapies have been explored in clinical trials, but they have yet to show significant therapeutic effects. Nevertheless, immunotherapy is inevitably the future of pancreatic cancer cure. This article introduces the current research progress and bottlenecks of immunotherapy for pancreatic cancer and puts forward further optimization directions and solutions. We hope to provide a reference for the future use of immunotherapy for pancreatic cancer.

Basic and Clinical Research Progress of Immunotherapy for Hepatocellular Carcinoma
Abstract:

Primary liver cancer, especially hepatocellular carcinoma, poses a serious threat to the life and health of the Chinese people. Given the insidious onset of liver cancer, less than 30% of hepatocellular carcinoma patients are considered for radical treatment at the initial diagnosis. Systemic anti-tumor therapy plays an important role in the treatment of advanced hepatocellular carcinoma. Immunotherapy of hepatocellular carcinoma has developed rapidly, and an increasing number of immunotherapy drugs, which can better control the progress of hepatocellular carcinoma and prolong the survival of patients, have become first- and second-line treatment options. This article reviews briefly the progress of immunotherapy for hepatocellular carcinoma in recent years.

Basic Research
Effects of Akkermansia on AOM/DSS Inflammatory-associated Colorectal Cancer
Abstract:
Objective 

To investigate the effects of Akkermansia muciniphila (AKK) on azomethane-oxide (AOM)/glucan sodium sulfate (DSS)-induced inflammatory colorectal cancer mouse model and intestinal stem cells.

Methods 

AOM/DSS-induced mouse models of inflammatory-associated colorectal cancer were randomly divided into three groups, namely, model, AKK and aspirin groups, based on different administration of drugs by gavage. The tumor number, size, distribution, and burden were observed 10 weeks after intervention. Immunohistochemical method was used to analyze the expressions of Ki67 and Lgr5 proteins, which are utilized to characterize tumor malignancy and stem cells. The mRNA expressions of Lgr5, CD133, Nanog, and ALDH1 were detected by qRT-PCR.

Results 

Compared with those of the model group, the tumor number, size, and burden of the AKK group were significantly reduced (P < 0.01). The expressions of Ki67 and Lgr5 in the AKK group of tumor tissues were significantly decreased (P < 0.05), and the mRNA expressions of CD133, Nanog and ALDH1 were significantly down-regulated.

Conclusion 

AKK is effective against AOM/DSS-induced colitis-associated colorectal cancer in mice, and its mechanism of action may be closely related to colorectal stem cell activity.

Effect of SMAC Gene on Sensitivity of Lung Adenocarcinoma Cells to Paclitaxel and Cell Viability Based on caspase-3/Bcl-2/Bax Signaling Pathway
Abstract:
Objective 

To investigate the effect of the SMAC gene on paclitaxel sensitivity and cellular activity in lung adenocarcinoma cells based on the caspase-3/Bcl-2/Bax signaling pathway.

Methods 

A paclitaxel-resistant cell line A549/Taxol was established for lung adenocarcinoma, and the cells were divided into four following groups: pcDNA-NC (transfected with pcDNA-NC blank vector), pcDNA-SMAC (transfected with pcDNA-SMAC vector), siRNA-NC (transfected with siRNA-NC empty virus vector), and siRNA-SMAC groups (transfected with siRNA-SMAC lentiviral vector). The SMAC mRNA expression in cells was detected by qRT-PCR; cell sensitivity was detected by MTT; cell proliferation ability was detected by cloning assay; cell invasion ability was detected by Transwell; apoptosis ability was detected by flow cytometry assay; and caspase-3, Bcl-2 and Bax protein expression in cells were detected by Western blot analysis.

Results 

The SMAC mRNA expression was significantly lower in A549 cells compared with BEAS-2B cells (P < 0.05). The SMAC mRNA expression was significantly higher in the pcDNA-SMAC group than that in the pcDNA-NC group cells (P < 0.05). The SMAC mRNA expression was significantly lower in the cells of the siRNA-SMAC group (P < 0.05) than that in the siRNA-NC group. The SMAC mRNA expression was significantly lower in the cells of the siRNA-SMAC group (P < 0.05) than in the siRNA-NC group. Compared with the pcDNA-NC group, the cell IC50, cell clone number, cell invasion ability, and Bcl-2 protein and Bcl-2/Bax ratio were significantly lower in the pcDNA-SMAC group, the cell resistance index reversal was 2.51-fold, and the apoptosis ability and caspase-3, as well as Bax protein expression, were significantly higher (P < 0.05). Compared with the siRNA-NC group, cell IC50, cell clone number, cell invasion ability, and Bcl-2 protein and Bcl-2/Bax ratio were significantly higher in the siRNA-SMAC group, and apoptosis ability and caspase-3 and Bax protein expression were significantly lower (P < 0.05).

Conclusion 

High expression of SMAC increases paclitaxel sensitivity, inhibits cell growth and invasion, promotes apoptosis in lung adenocarcinoma cells, and has a regulatory effect on the caspase-3/Bcl-2/Bax signaling pathway.

Clinical Research
Treatment and Outcome of Merkel Cell Carcinoma in A Single Center
Abstract:
Objective 

To investigate the clinical features, treatment, and outcome characteristics of patients with Merkel cell carcinoma.

Methods 

The clinical manifestations, laboratory tests, diagnosis and treatment, and follow-up data of six patients with Merkel cell carcinoma were retrospectively analyzed.

Results 

Among the six patients with Merkel cell carcinoma, four were males and two were females, with a median age of 66 years old (57-76 years old). All six patients presented with skin swelling, and the clinical stages were as follows: stageⅠ in three patients, stage Ⅲ in one patient, and stage IV in two patients. Two patients were treated with surgery alone, three patients with surgery combined with radiotherapy and/or chemotherapy, and one patient with immunotherapy combined with chemotherapy. Until the follow-up time, four patients had no disease progression, one patient died because of disease progression, and one patient remained under treatment.

Conclusion 

Limited-stage Merkel cell carcinoma is primarily treated with surgery and radiotherapy, meanwhile, metastatic Merkel cell carcinoma needs systemic therapy, and first-line immune checkpoint inhibitors targeting PD-1/ PD-L1 pathway can achieve better therapeutic results.

Prognostic Analysis of Socioeconomic Factors in Multiple Myeloma Patients and Construction of A Myeloma-specific Survival Prediction Model
Abstract:
Objective 

To investigate the effects of socioeconomic factors on the prognosis of multiple myeloma (MM) patients and construct a prediction model for evaluating myeloma-specific survival (MSS) rates.

Methods 

A total of 32625 patients diagnosed with MM between January 2007 and December 2016 were included through the SEER database. Cox regression model was used to analyze the predictive indicators of MSS. The results of the multivariate subgroup analysis were presented as forest plots. The significant factors identified in the multivariate Cox analysis were used to construct a nomogram. The predictive performance of the nomogram was assessed using the AUC and calibration plots. A nomogram score-based risk stratification system was constructed using a restricted cubic spline.

Results 

Patients were divided into five groups according to their socioeconomic status (SES). Groups with higher SES had relatively higher proportions of those part of the White, insured, married, and urban populations. Age, gender, race, marital status, insurance status, and SES were independent prognostic factors of MSS (all P < 0.001). The linear trend of increased MSS risk with decreasing SES was most pronounced among the White, married, insured, and urban patients (all P < 0.001). The nomogram exhibited good discrimination and accuracy in both training and validation sets, showing AUC values of 0.701, 0.709, and 0.722 for predicting 3-, 5-, and 8-year MSS, respectively. A risk stratification model was established based on the nomogram total points and the HR, which then divided patients into three different risk levels with substantial survival disparities (all P < 0.001).

Conclusion 

Socioeconomic factors, such as marital status, insurance status, and SES, have a significant impact on the survival outcomes of MM patients. The nomogram and the risk stratification model based on these factors can accurately and reliably predict MSS.

Short-Term Efficacy and Postoperative Inflammatory Cytokine Changes in Lung Cancer Treated with Da Vinci Robot-assisted Versus Video-assisted Thoracoscopic Surgery
Abstract:
Objective 

To evaluate the short-term outcomes and postoperative inflammatory cytokine changes in patients with lung cancer treated with robot-assisted thoracoscopic surgery (RATS) versus video-assisted thoracoscopic surgery (VATS).

Methods 

A total of 270 patients with lung cancer treated by minimally invasive surgery were selected for the study, and the surgical procedures were selected according to the patients' economic conditions and preferences. Among them, 132 patients completed the operation through RATS, and 138 patients completed the operation through VATS. The clinical data of the two groups were compared.

Results 

All patients successfully completed radical lung cancer surgery, and no perioperative deaths were reported. Intraoperative bleeding, postoperative drainage time, postoperative hospital stay, number of lymph nodes dissected, and number of lymph nodes dissected groups were more advantageous in the RATS group compared with the VATS group (P < 0.05). In terms of operative time, total postoperative chest drainage, and hospitalization cost, the VATS group had an advantage (P < 0.05). The postoperative levels of CRP, PCT, IL-6, IL-8, IL-10, and TNF-α increased in both groups, compared with preoperative levels, and the increases in the RATS group were lower than those in the VATS group.

Conclusion 

RATS offers technical and short-term efficacy advantages for the treatment of lung cancer but comes with the disadvantage of high cost. Post-operative inflammatory cytokine elevation is lower in the RATS group, and inflammatory response to the organism is less severe.

Construction and Validation of A Risk Model for Predicting Prognosis and Immunotherapy Response of Bladder Cancer Based on Cellular Senescence-related Genes
Abstract:
Objective 

To evaluate the prognosis and immunotherapy response of patients with bladder cancer by constructing a risk-score model of cellular senescence-related signature (SRS), as well as to explore the clinical application value of SRS in bladder cancer.

Methods 

Senescence genes were screened from TCGA-BLCA, and cellular SRS genes were screened according to LASSO regression. A bladder cancer risk-score model was constructed based on the SRS genes to analyze the survival difference and model-fit degree of TCGA-BLCA high- and low-risk groups. Univariable and multivariable Cox regression was used to analyze the prognostic risk factors of bladder cancer. Overall survival differences of high- and low-risk groups in GEO-BLCA database were verified, and variations in immunotherapy responses were analyzed in IMvigor210 databases. According to the result of β-gal chromogenic reaction in bladder cancer and normal paracancer tissues, the existence of cell senescence was determined.

Results 

Eight marker genes were screened, and patients were divided into high- and low-risk groups according to the median risk score constructed by the marker genes. The 5-year survival rate of high risk group was lower than that of low risk group (training and validation sets P < 0.05). The area under the ROC curve of TCGA-BLCA in 1-, 3-, and 5-year were 0.657, 0.660, and 0.688, and those for GSE13507 were 0.665, 0.665, and 0.613, respectively. SRS risk score can be used as an independent risk factor for the prognosis of patients with bladder cancer. The SRS risk score in the response group was lower than that in the non-response group during bladder cancer immunotherapy (P < 0.05). The β-gal staining of bladder cancer tissue was positive, but the β-gal staining of adjacent normal tissue was negative.

Conclusion 

Cell senescence occurs in bladder cancer tissues. SRS risk score can predict the clinical prognosis of patients with bladder cancer, and patients with low score can benefit from immunotherapy. SRS is a reliable biomarker for the prognosis and immunotherapy response of bladder cancer.

Clinical Diangnosis
AI Cytomorphology Combined with DNA-image Cytometry for Identifying Benign and Malignant Pleural Effusion and Ascites
Abstract:
Objective 

To explore the diagnostic value of artificial intelligence (AI) cytology combined with DNA-image cytometry (DNA-ICM) auxiliary diagnostic system for the identification of benign and malignant pleural effusion and ascites.

Methods 

Liquid-based cytology technology (LCT), DNA-ICM, AI, and AI combined with DNA-ICM were used to identify benign and malignant pleural effusion and ascites specimens in 360 cases, and their sensitivity, specificity, accuracy, Kappa value, Youden index and AUC were statistically analyzed.

Results 

The sensitivity, specificity, and accuracy of AI combined with DNA-ICM in detecting benign and malignant pleural effusion and ascites were 95.23%, 94.12%, and 94.44%, respectively, which were higher than those of the three other separate detection methods (all P < 0.05). The kappa values of LCT, DNA-ICM, and AI were 0.646, 0.642, and 0.586; their Youden index values were 0.693, 0.687, and 0.676, and their AUC values were 0.846, 0.843, and 0.838, respectively. The Kappa value of AI combined with DNA-ICM was 0.869, the Youden index was 0.893, and AUC was 0.947, which were all higher than those of the three detection methods alone.

Conclusion 

Among the three separate detection methods, LCT has the highest reliability, authenticity, and diagnostic value, and it can be used as a common method for the clinical identification of benign and malignant pleural effusion and ascites. The diagnostic performance of AI combined with DNA-ICM auxiliary diagnosis system in identifying benign and malignant pleural effusion and ascites is better than those of the three separate detection methods and can be used as a reliable method for the clinical identification of benign and malignant pleural effusion and ascites.

Effect of Photodynamic Therapy for Malignant Obstruction of Biliary Tract
Abstract:
Objective 

To investigate the safety and efficacy of photodynamic therapy (PDT) for malignant obstruction of the biliary tract.

Methods 

We retrospectively analyzed the clinical data of patients with malignant biliary obstruction treated by PDT in our medical center. On the basis of different treatment plans, the patients were categorized into the photodynamic only group and the combined treatment group, in which additional interventional operations, targeted therapy, or immunotherapy were arranged. The alterations in liver function, duration of biliary patency, and postoperative complications that occurred within one month were closely monitored in both groups.

Results 

A total number of 19 patients were enrolled in this study. The technical success rate of PDT was 100%. The deterioration of liver function was not observed in any patients within one month after PDT. Within a maximum of 17.7 months follow-up, the patency rates of the biliary tract were 100.0%, 89.5%, 72%, and 64% at 1, 3, 6, and 12 months after the procedure, respectively. The mean biliary patency time was 6.9±0.8 months (95%CI: 5.2-8.7 months). Specifically, the biliary patency times for Bismuth type Ⅲ and Ⅳ were 7.5±1.1 and 6.1±1.3 months, respectively. The biliary patency time was around 3.3±0.7 months in the photodynamic only group and 7.9±0.9 months in the combined treatment group (P=0.017).

Conclusion 

PDT for Bismuth Ⅲ-Ⅳ malignant biliary obstruction is safe and effective. Moreover, the period of biliary patency is greatly extended when PDT is combined with systemic therapy.

Reviews
Research Progress of Macropinocytosis in Digestive System Tumors
Abstract:

Macropinocytosis, an evolutionarily conserved, actin-dependent form of endocytosis, is involved in various physiological processes, including nutrient absorption, antigen presentation, and cell signaling transduction and migration. Oncogene activation and tumor suppressor inactivation induce macropinocytosis in tumors in the digestive system, involved in tumorigenesis and progression, whereas the inhibition of macropinocytosis slows the aggressive phenotype of digestive system tumors and improves the efficacy of anti-tumor drugs. Macropinocytosis can also be used as a delivery route for anti-tumor drugs. Therefore, macropinocytosis has been widely studied to develop new methods for the treatment of digestive system tumors.This paper reviews the role of macropinocytosis in the body, the regulation of macropinocytosis-related signaling pathway, as well as the mechanism of macropinocytosis in colorectal cancer, pancreatic ductal adenocarcinoma, liver cancer and other digestive system tumors, to provide reference for related researches.

Research Progress on Role of Probiotic Akkermansia Muciniphila in Oncogenesis, Development and Treatment of Tumor
Abstract:

Although tumor treatment models have been continuously improved in clinical practice, cancer remains a serious threat to human health. The effect of probiotics on tumor therapy has received extensive attention. As a common colonizer of the intestinal mucosa, Akkermansia muciniphila(AKK) has a well-defined role in metabolic diseases, but its complex role in tumor development and therapeutic efficacy has not been fully elucidated. The unique properties and physiological roles of AKK play an important role in different solid tumors and it may be a potential biomarker. This article provides a review of previous studies and proposes clinical strategies to influence the abundance of AKK to provide a theoretical reference for the development of next-generation probiotics and the reshaping of the tumor treatment landscape.

Progress in Development of Targeted Therapeutic Drugs for Acute Myeloid Leukemia
Abstract:

Targeted therapeutic drugs for acute myeloid leukemia (AML) are showing immense development, thereby laying a solid foundation for the precise treatment of AML patients. The paper reviews four types of targeted drugs that have progressed rapidly for AML treatment (by targeting genes or signaling-pathway alterations, targeting apoptosis-related pathways, targeting cell-surface antigens, and targeting immune-related substances). We look forward to the future development directions of targeted drugs, providing references for hematologists and developers of new drugs for AML.

Advances on Clinical Application of Adaptive Radiotherapy in Treatment of Nasopharyngeal Carcinoma
Abstract:

Radiotherapy is the first treatment choice for nasopharyngeal carcinoma. With the rapid development of image-guided radiotherapy, adaptive radiotherapy (ART) has become widely available in clinical practice. ART may be implemented to monitor the anatomical or physiological variations of patients using dynamic imaging technology and feedback information during the treatment course, including geometric changes (size, shape, and position) of tumor and normal organs. ART also allows the modification of the treatment plan to accurately deliver the maximize dose to target and minimize normal tissue explosion. This review discusses the physics basis of ART and its state-of-art application and potential pitfalls.

Guidelines & Interpertation
Interpretation of Expert Consensus on Diagnosis and Treatment of Cutaneous Basal Cell Carcinoma (2021) by A Multidisciplinary Team
Abstract:

Basal cell carcinoma (BCC) is the most common malignant tumor in dermatology with incidence rising rapidly. Expert consensus on diagnosis and treatment of cutaneous basal cell carcinoma (2021) was published in September 2021 by Skin Tumor Research Center, Chinese Society of Dermatology and Subcommittee on Skin Tumor, China Dermatologist Association. This consensus comprehensively describes the epidemiology, pathogenesis, clinical manifestations, auxiliary examination, pathology, pretreatment assessment, treatment, prognosis, and follow-up education. It offers an important guideline for promoting the standardized diagnosis and treatment of skin BCC in China. In this work, multidisciplinary experts interpreted the main contents of the consensus, including clinicopathological findings, pretreatment assessment, and treatment advance.

Case Report
Morphological and Immunophenotypic Tendency of AML-M2 in Acute Promyelocytic Leukemia: A Case Report
Tumor Information
Robot-assisted Microwave Ablation for Lung Tumors Originated by The Chinese University of Hong Kong, etc