Objectives Objectives To investigate how the imbalance of innate lymphoid cells (ILCs)in the peripheral blood of patients with lung adenocarcinoma affects the balance of downstream mononuclear macrophages and T helper (Th) cells, and to identify the impact of the imbalance of ILCs on the immune status and prognosis of lung adenocarcinoma. Methods The peripheral blood of 20 patients with lung adenocarcinoma and normal controls were collected. The percentage of ILCs, mononuclear macrophages and T lymphocyte in peripheral blood were analyzed by flow cytometry. The characteristic cytokine secretion levels of various types of immune cells in peripheral blood were detected by real-time fluorescence quantitative PCR. Results Compared with the normal controls, the proportion of M2 mononuclear macrophages, ILC1 and ILC2 in patients with lung adenocarcinoma was up-regulated, while the proportion of M1 mononuclear macrophages, CD4⁺ T and CD8⁺ T was down-regulated. The mRNA expression of related cytokines of M1 mononuclear macrophages and ILC1 were decreased; while the mRNA expression of related cytokines of M2 mononuclear macrophages and ILC2 were increased. Along with the decreased CD4⁺T cells-associated cytokine T-bet mRNA expression, and the increased GATA3 mRNA expression. Moreover, the expression of PD-1 in CD8⁺ T cells was also up-regulated. Conclusion The imbalance of ILCs in peripheral blood of patients with lung adenocarcinoma promotes the imbalance of mononuclear macrophages and Th cells, which altogether maintains the immunosuppression in patients with lung adenocarcinoma, and promotes the development of lung adenocarcinoma.
Humans ; Lymphocytes ; Immunity, Innate ; CD8-Positive T-Lymphocytes ; Cytokines/metabolism* ; Adenocarcinoma of Lung ; Immunosuppression Therapy ; RNA, Messenger

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).
Male ; Humans ; Aged ; Pancreatic Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Adenocarcinoma ; Neoplasm Recurrence, Local/surgery* ; Immunotherapy ; Liver Neoplasms/therapy* ; Pancreatectomy

A patient with advanced lung adenocarcinoma developed symptoms of frequent urination and urgent urination after 14 cycles of Pembrolizumab combined with chemotherapy. After making comprehensive analysis of the results of urine routine test, renal function, cystoscope and computed tomography (CT) examination, immune checkpoint inhibitors related cystoureteritis and acute kidney injury were considered. The patient's symptoms were relieved after discontinuation of Pembrolizumab combined with chemotherapy. However, the symptoms of urinary irritation worsened significantly after rechallenging Pembrolizumab combined with chemotherapy, and the symptoms was relieved after corticosteroids treatment. If patients develop urinary symptoms during immune checkpoint inhibitors treatment, immune checkpoint inhibitors related cystoureteritis should be considered for early differential diagnosis in order to implement appropriate treatment.
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Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/pathology* ; Adenocarcinoma of Lung/drug therapy* ; Tomography, X-Ray Computed

Objective: To analyzed perioperative safety of cytoreductive surgery (CRS) for patients with colorectal cancer peritoneal metastasis (CRPM) and to construct a predictive model for serious advese events (SAE). Methods: A descriptive case-series study was conducted to retrospectively collect the clinicopathological data and treatment status (operation time, number of organ resection, number of peritoneal resection, and blood loss, etc.) of 100 patients with peritoneal metastases from colorectal cancer or appendix mucinous adenocarcinoma who underwent CRS at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to August 2021. There were 53 males and 47 females. The median age was 52.0 (39.0-61.8) years old. Fifty-two patients had synchronous peritoneal metastasis and 48 had metachronous peritoneal metastasis. Fifty-two patients received preoperative neoadjuvant therapy. Primary tumor was located in the left colon, the right colon and the rectum in 43, 28 and 14 cases, respectively. Fifteen patients had appendix mucinous adenocarcinoma. Measures of skewed distribution are expressed as M (range). Perioperative safety was analyzed, perioperative grade III or higher was defined as SAE. Risk factors associated with the occurrence of SAEs were analyzed using multivariate logistic regression. A nomogram was plotted by R software to predict SAE, the efficacy of which was evaluated using the area under the ROC curve (AUC) and correction curves. Results: The median peritoneal cancer index (PCI) score was 16 (1-39). Sixty-eight (68.0%) patients achieved complete tumor reduction (tumor reduction score: 0-1). Sixty-two patients were treated with intraperitoneal hyperthermic perfusion chemotherapy (HIPEC). Twenty-one (21.0%) patients developed 37 SAEs of grade III-IV, including 2 cases of ureteral injury, 6 cases of perioperative massive hemorrhage or anemia, 7 cases of digestive system, 15 cases of respiratory system, 4 cases of cardiovascular system, 1 case of skin incision dehiscence, and 2 cases of abdominal infection. No grade V SAE was found. Multivariate logistic regression analysis showed that CEA (OR: 8.980, 95%CI: 1.428-56.457, P=0.019), PCI score (OR: 7.924, 95%CI: 1.486-42.259, P=0.015), intraoperative albumin infusion (OR: 48.959, 95%CI: 2.115-1133.289, P=0.015) and total volume of infusion (OR: 24.729, 95%CI: 3.956-154.562, P=0.001) were independent risk factors for perioperative SAE in CRS (all P<0.05). Based on the result of multivariate regression models, a predictive nomogram was constructed. Internal verification showed that the AUC of the nomogram was 0.926 (95%CI: 0.872-0.980), indicating good prediction accuracy and consistency. Conclusions: CRS is a safe and effective method to treat CRPM. Strict screening of patients and perioperative fluid management are important guarantees for reducing the morbidity of SAE.
Adenocarcinoma, Mucinous/therapy* ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Appendiceal Neoplasms/surgery* ; Colorectal Neoplasms/pathology* ; Combined Modality Therapy ; Cytoreduction Surgical Procedures/methods* ; Female ; Humans ; Hyperthermia, Induced/methods* ; Male ; Middle Aged ; Peritoneal Neoplasms/secondary* ; Retrospective Studies ; Survival Rate

Objective: To compare the prognostic influence and postoperative pathology of different comprehensive treatment models for adenocarcinoma of esophagogastric junction. Methods: Between January 2012 and December 2017, a total of 219 patients with adenocarcinoma of esophagogastric junction underwent surgery in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute and were enrolled in this study. The clinicopathological data of these patients were collected. The patients were categorized into 3 groups according to different treatment models: surgery-first group, neoadjuvant chemotherapy (NAC) group and neoadjuvant chemoradiotherapy (nCRT) group. A trimatch propensity score analysis was applied to control potential confounders among the three groups by using R language software. A total of 7 covariates including gender, age, comorbidity, body mass index, clinical T stage, clinical N stage and Siewert type were included, and the caliper value was taken as 0.2. After matching, a total of 87 patients were included for analysis with 27 patients for each group. There were 82 males and 5 females, with a median age of 63 years (range: 38 to 76 years). The effect of preoperative treatment on postoperative tumor pathology among the three different comprehensive treatment models was explored by χ² test, ANOVA or Wilcoxon rank sum test. Mann-Whitney U test or χ² test were used to undergo pairwise comparisons. Kaplan-Meier method and Log-rank test were used to analyze the overall survival and progression-free survival. Results: The proportion of vascular embolism in the surgery-first group was 72.4% (21/29), which was significantly higher than NAC group (37.9% (11/29), χ²=6.971, P=0.008) and nCRT group (6.9% (2/29), χ²=26.696, P<0.01). The proportions of pathological T3-4 stage in nCRT group and NAC group were 55.2% (16/29) and 62.1% (18/29), respectively, which were significantly lower than the surgery-first group (93.1% (27/29), χ²=10.881, P=0.001; χ²=8.031, P=0.005). Compared with the NAC group (55.2% (16/29), χ²=6.740, P=0.009) and nCRT group (31.0% (9/29), χ²=18.196, P<0.01), the proportion of lymph node positivity 86.2% (25/29) were significantly higher in the surgery-first group. The 5-year overall survival rates were 62.1%, 68.6% and 41.4% for the surgery-first group, NAC group and nCRT group, respectively (χ²=4.976, P=0.083). The 5-year progression-free survival rates were 61.7%, 65.1% and 41.1% for the surgery-first group, NAC group and nCRT group, respectively. The differences in overall survival (χ²=4.976, P=0.083) and progression-free survival (χ²=4.332, P=0.115) among the three groups were nonsignificant. Conclusions: Postoperative pathology is significantly different among the three groups. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy could decrease the proportions of vascular embolism, pathological T3-4 stage and lymph node positivity to achieve local tumor control. The prognosis of overall survival and progression-free survival are not significantly different among the three groups.
Adenocarcinoma/pathology* ; Adult ; Aged ; Cohort Studies ; Esophagogastric Junction/pathology* ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Propensity Score

The number of minimally invasive surgery (MIS) for adenocarcinoma of esophagogastric junction (AEG) has been increasing year by year. The key technical points such as surgical approach, lymph node dissection and GI tract reconstruction have gradually reached their maturity. With the emergence of proofs of evidence-based neoadjuvant therapy, neoadjuvant chemotherapy or neoadjuvant radiochemotherapy for advanced AEG is also gradually accepted by most surgeons and oncologists. European scholars have previously started researches on MIS after neoadjuvant therapy for esophageal cancer and AEG. Domestic scholars also raise practical suggestions on the application of neoadjuvant therapy for AEG via the cooperation between gastrointestinal and thoracic surgeons, demonstrating the trend in standardization and individualization. But there is still no consent to the indication of MIS after neoadjuvant therapy. Furthermore, there is also a lack of the standardization of technical points for MIS, GI tract reconstruction, short- and long-term outcomes. Such associated problems have been the hot controversy and exploration in recent years. This article describes current progress of neoadjuvant therapy for AEG, current status of MIS after the neoadjuvant therapy in Europe, America, East Asia, including China, and related researches plus future prospects, hoping for better clinical outcomes.
Adenocarcinoma/surgery* ; Esophageal Neoplasms/surgery* ; Esophagogastric Junction/surgery* ; Humans ; Minimally Invasive Surgical Procedures ; Neoadjuvant Therapy ; Stomach Neoplasms/surgery*

Adenocarcinoma, Follicular/diagnosis* ; Diagnosis, Differential ; Humans ; Metabolomics ; Thyroid Neoplasms/therapy*

Cancer is one of the most devastating diseases worldwide and definitive therapeutics for treating cancer are not yet available despite extensive research efforts. The key challenges include limiting factors connected with traditional chemotherapeutics, primarily drug resistance, low response rates, and adverse side-effects. Therefore, there is a high demand for novel anti-cancer drugs that are both potent and safe for cancer prevention and treatment. Gallic acid (GA), a natural botanic phenolic compound, can mediate various therapeutic properties that are involved in anti-inflammation, anti-obesity, and anti-cancer activities. More recently, GA has been shown to exert anti-cancer activities via several biological pathways that include migration, metastasis, apoptosis, cell cycle arrest, angiogenesis, and oncogene expression. This review discusses two aspects, one is the anti-cancer potential of GA against different types of cancer and the underlying molecular mechanisms, the other is the bibliometric analysis of GA in cancer and tumor research. The results indicated that lung cancer, prostate cancer, stomach cancer, and colon adenocarcinoma may become a hot topic in further research. Overall, this review provides evidence that GA represents a promising novel, potent, and safe anti-cancer drug candidate for treating cancer.
Adenocarcinoma/drug therapy* ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; Cell Line, Tumor ; Colonic Neoplasms ; Gallic Acid/therapeutic use* ; Humans ; Male

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.
Adenocarcinoma of Lung/drug therapy* ; Adrenocorticotropic Hormone/therapeutic use* ; Aged ; B7-H1 Antigen/therapeutic use* ; Humans ; Hydrocortisone/therapeutic use* ; Hyponatremia/drug therapy* ; Hypopituitarism/drug therapy* ; Immune Checkpoint Inhibitors ; Lung Neoplasms/pathology* ; Male ; Methylprednisolone/therapeutic use* ; Middle Aged ; Nausea/drug therapy* ; Pituitary Gland/pathology* ; Pneumonia ; Prednisone/therapeutic use* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Prolactin/therapeutic use*

Esophageal cancer (EC) has a high incidence and poor prognosis. The two major histological types, squamous cell carcinoma and adenocarcinoma, differ in their epidemiology and treatment options. Patients with locally advanced EC benefit from multimodal therapy concepts including neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy, and perioperative chemotherapy. Currently, immunotherapy for the solid tumor is a hot spot. Treatment with adjuvant immune checkpoint inhibitors (ICIs) is the first immunotherapy for resectable EC listed in the latest National Comprehensive Cancer Network Guidelines for the Esophageal and Esophagogastric Junction Cancers. Recent clinical trials have established ICIs for three treatment models of resectable EC. Their short-term results demonstrated ideal efficacy and tolerable toxicity, though some concerns remain. This review summarizes the novel data on the ICIs for resectable EC and lists the registered related clinical trials. Hopefully, this review can provide a reference for ongoing research on the treatment options for resectable EC.
Humans ; Esophageal Neoplasms/pathology* ; Esophagogastric Junction/pathology* ; Neoadjuvant Therapy/methods* ; Adenocarcinoma/drug therapy* ; Immunotherapy