AIM: To investigate the effects of age, gender, duration of medication and combined medication on the steady-state blood concentration of tacrolimus in patients with autoimmune diseases, and to establish the reference range of steady-state blood concentration of tacrolimus in combination with liver and kidney function, so as to provide theoretical basis for clinical individual medication. METHODS: A total of 107 patients with autoimmune diseases treated with tacrolimus in the department of rheumatology and immunology of our hospital from August 2017 to June 2021 were included. Their gender, age, dose, drug combination, blood concentration, and liver and kidney function were statistically analyzed by SPSS 22.0 statistical software. RESULTS: In the treatment of autoimmune diseases with tacrolimus, there was statistical significance in the blood concentration of different genders (P<0.05), but there was no statistical significance in the blood concentration of different ages (P>0.05) and a statistically significant difference in the dosage of tacrolimus (P<0.05), the duration of medication did not affect the effective dose, target blood concentration, liver and kidney functions. There was a weak correlation between tacrolimus dose and blood concentration (r=0.115, P=0.047). When the blood concentration of tacrolimus ranged from 4.20 to 9.48 ng/mL, the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea increased significantly. When tacrolimus blood concentration ranged from 0.08 to 4.20 ng/mL, there was no significant difference in serum creatinine, AST, ALT, albumin, total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL). CONCLUSION: Tacrolimus is used for the treatment of autoimmune diseases, and the blood concentration varies greatly among individuals. To avoid the risk of potential damage to liver and kidney function. It is recommended that clinicians control the blood concentration at 0.08-4.20 ng/mL, and adjust the dose and optimize the dose according to the patient's gender, age, and clinical efficacy.

Objective To analyze the clinical efficacy,toxicity and survival prognosis of patients diagnosed with Siewert type Ⅱ and Ⅲ locally advanced adenocarcinoma of esophagogastric junction (AEG) undergoing preoperative involved-field irradiation with concurrent chemotherapy. Methods A total of 45 cases were recruited in this prospective clinical trial. Prior to surgery, patients received 2 cycles of chemotherapy with XELOX and concurrent radiotherapy ( a total of 45 Gy in 25 fractions,5 times weekly). After 6-8 weeks,they underwent surgical resection. After the surgery,patients received 6 cycles of adjuvant chemotherapy. The completion of preoperative neoadjuvant chemoradiotherapy, postoperative pathological status,TNM down-staging effect and adverse reactions were observed. Kaplan-Meier method was applied to estimate survival analysis. Results All 45 patients completed preoperative neoadjuvant chemoradiotherapy. Among them, 39 patients completed 2 cycles of chemotherapy, and 6 patients completed 1 cycle of chemotherapy. The median time of surgical interval was 6 weeks. The R0resection rate was 96%.The pathological complete response (pCR) rate was 22%. The TNM down-staging rate was 69%.The incidence of acute radiation-induced esophagitis or gastritis was 44% and the incidence of radiation-induced pneumonitis was 7%. The incidence of grade 1-3 leukocytopenia,thrombocytopenia and neutropenia was 78%,47% and 44%,respectively. In terms of gastrointestinal reactions,the incidence of nausea,vomiting and loss of appetite was 62%,24% and 71%,respectively. No hematologic or nonhematologic adverse effects was observed at grade 4 or 5.The median follow-up time was 30 months. 11 patients died of cancer,1 patient was treatment-related death in the perioperative period and 1 patient died of pneumonia. The 1-,2-and 3-year progression-free survival (PFS) rates were 90%,70% and 67%,respectively. The 1-,2-and 3-year overall survival rates were 95%,80% and 75%,respectively. The 1-,2-and 3-year local control rates were 95%,84% and 84%, respectively. The 1-, 2-and 3-year distant metastasis rates were 7%, 25% and 25%, respectively. Conclusions Preoperative involved-field irradiation with concurrent chemotherapy yields relatively high clinical efficacy and is well tolerated by patients with Siewert typeⅡandⅢlocally advanced AEG.Patients are recommended to receive 4 cycles of adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery.

Objective To examine the effects of different pre-treatment nutritional status and inflammatory markers on acute adverse reactions in esophageal cancer patients during concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy.Methods The acute adverse reactions of 338 eligible esophageal cancer patients who received concurrent IMRT and chemotherapy in our hospital from 2006 to 2014 were reviewed.The effects of different pre-treatment nutritional status, such as body mass index level (BMI), albumin level (ALB), total lymphocyte count (TLC), the presence or absence of anemia, and inflammatory indicators including neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), on acute adverse reactions in the patients were examined.Data were analyzed using the chi-square test with continuity correction and logistic regression analysis.Results The incidence rate of malnutrition in the patients based on their nutritional status was 5.62%-54.14%.The incidence rate of grade≥2 acute radiation esophagitis (RE) was significantly higher in the low ALB group than in the normal ALB group (P=0.000).The incidence rate of adverse reactions in the hematologic system increased as TLC decreased (P=0.006), but the incidence rate of acute radiation pneumonitis (RP) was reduced as TLC decreased (P=0.001).In addition, the incidence rate of grade ≥2 acute RE was significantly higher in the anemia group than in the non-anemia group.Inflammatory marker analysis demonstrated that the incidence rate of acute RE was significantly higher in the high NLR group and high PLR group than in the low NLR group and low PLR group (P=0.000 and P=0.024, respectively).Logistic regression analysis of nutritional status and inflammatory markers showed that TLC was an independent risk factor for acute adverse reactions in the hematologic system (P=0.001), and ALB and PLR were independent risk factors for acute RE (P=0.017 and P=0.011,respectively).Conclusions Nutritional status and inflammatory markers are associated with concurrent chemoradiotherapy-induced acute adverse reactions in esophageal carcinoma patients, and hence may be valuable indicators of acute adverse reactions during treatment.In addition, nutritional treatment and support care should be actively provided to the patients to prevent the development of acute adverse reactions during treatment.

Objective To investigate the clinical effect of induction chemotherapy plus concurrent radiochemotherapy in the treatment of locally advanced non-small cell lung cancer (NSCLC) through a meta-analysis.Methods CBM, CNKI, Cochrane Library, PubMed, and EMbase were searched for the articles on comparison between induction chemotherapy plus concurrent radiochemotherapy and concurrent radiochemotherapy for patients with locally advanced NSCLC.According to the inclusion and exclusion criteria, the data on short-term outcome and survival were collected.A Meta-analysis was performed to evaluate the clinical effect of induction chemotherapy followed by concurrent radiochemotherapy.Results A total of 5 articles were included, which involved 845 patients.The results showed that the short-term outcome and the 2-and 3-year survival rates were similar between patients receiving induction chemotherapy plus concurrent radiochemotherapy and those receiving concurrent radiochemotherapy ( OR=0.875, 95% CI 0.507-1.510, P=0.631;HR=0.770, 95% CI 0.515-1.151, P=0.203;HR=0.809, 95% CI 0.559-1.172, P=0.262), but the patients receiving induction chemotherapy plus concurrent radiochemotherapy showed a significantly higher incidence rate of grade ≥ 3 leukopenia than those receiving concurrent radiochemotherapy alone ( OR=0.637, 95% CI 0.435-0.931, P=0.020).Conclusions Induction chemotherapy plus concurrent radiochemotherapy shows no significant advantages over concurrent radiochemotherapy alone in the short-term outcome and 2-and 3-year survival rates, but it significantly increases myelosuppression.Since there are few studies involving a limited number of cases included in this analysis, more multicenter randomized trials are needed to provide more detailed data and further clarify the clinical value of induction chemotherapy plus concurrent radiochemotherapy.

Objective To investigate the clinicopathological characteristics, patterns of lymph node metastasis and the influencing factors in esophageal adenocarcinoma. Methods A total of 201 cases of esophageal adenocarcinoma were selected for this study, including 89 cases of pure adenocarcinoma, 57 cases of adenoacanthoma cell carcinoma, 33 cases of mucoepidermoid carcinoma and 22 cases of adenoid cystic carcinoma. A total of 2026 lymph nodes were dissected with an average of 10 lymph nodes. The rule of lymph node metastasis in patients with esophageal adenocarcinoma was analyzed, and the risk factors for lymph node metastasis were identified. Results Esophageal adenocarcinoma in the middle thoracic esophagus accounted for 50.7% of all patients, and 43.8% in the lower thoracic esophagus. Ninety out of 201 cases (44.8%) had lymph node metastasis. 322 lymph nodes were positive for metastatic adenocarcioma with a metastatic ratio of 15.9% (322/2026).Among the patients with upper?thoracic esophageal carcinoma, 9.1% (1/11) of the cases had lymph node metastasis in the superior mediastinum but no lymph node metastasis was found in the middle mediastinum, lower mediastinal and abdominal lymph nodes. The middle?thoracic esophageal adenocarcinoma showed more extensive lymph node metastasis. Lower mediastinal and abdominal lymph node metastases were common in lower?thoracic esophageal cancer. Multivariate analysis showed that gender, length of lesion, depth of invasion and vascular invasion were independent risk factors for lymph node metastasis in esophageal adenocarcinoma ( P=0. 010, P=0. 006, P=0. 000, P=0. 019, respectively) . Male patients had more lymph node metastasis than female patients ( 49. 1% vs 26. 3%, P=0.011). The rates of lymph node metastasis in the tumor length ≤3 cm group, 3.1?5 cm group and >5 cm group were 20.4%, 42.9% and 65.7%, respectively. Lymphatic metastasis rates in the T1, T2, T3, T4 stage cancers were 7.1%, 36.8%, 38.1% and 69.4%, respectively, (P<0.001). Patients with vascular invasion had a higher rate of lymph node metastasis ( 73. 9%) than the patients without vascular invasion (41.0%) (P=0.003). Conclusions Most of the esophageal adenocarcinoma are distributed in the middle thoracic esophagus, followed by that in the lower thoracic segment. The lymph node metastasis rate, lymph node metastasis ratio and pattern of lymph node metastasis are similar to those of esophageal squamous cell carcinoma. Male, tumor length, depth of invasion and vascular invasion are risk factors of lymph node metastasis for patients with esophageal adenocarcinoma.

Objective To explore the patterns and influencing factors of lymph node metastasis of adenocarcinoma of the esophagogastric junction ( AEG ) . Methods Clinicopathological data of 393 AEG patients who underwent radical resection and lymphadenectomy in the thoracic or abdominal cavity were collected. We analyzed the metastatic patterns of 5 119 excised lymph nodes with an average of 13 nodes per patient according to Siewert classification, and the associations between lymphatic metastasis and clinicopathological factors, such as tumor invasion, differentiation, maximum diameter, or pathological type were analyzed. Results The lymph node metastasis rate and ratio ( LNR) were 70. 0% ( 275/393) and 29.1% (1 492/5 119), respectively. All the Siewert subtypes of AEG mainly metastasize downwards to the abdominal lymph nodes, while also spread upwards to the mediastinal lymph nodes. Among them, the lymph node metastasis rate was highest in Siewert type Ⅰ and lowest in Siewert type Ⅲ AEG. The lymph node metastasis rate and ratio in T1, T2, T3, T4 AEGs were 0%, 29. 4%, 75. 0%, 74. 6% and 0%, 10. 1%, 14.2%, 32.0%,respectively (χ2=35.305,P<0.001 andχ2=134.034,P<0.001) . The lymph node metastasis rate and ratio of the poorly differentiated adenocarcinoma were 36.0% and 79.3%, respectively, significantly higher than 22.1% and 61.7% of the well?differentiated adenocarcinoma (χ2=14.468, P<0.001 and χ2=120.009, P<0.001). The lymph node metastasis rate and ratio of patients with a tumor in maximum diameter≥4 cm were 73.1% and 30.9%, significantly higher than 46.8% and 14.6%, respectively, in the patients with a tumor in maximum diameter of<4 cm (χ2=13.636, P<0.001 andχ2=64.767, P<0.001) . The group of vascular tumor thrombus showed significantly higher lymph node metastasis rate and ratio than those in the group with no vascular tumor thrombus ( 84. 6% versus 67. 1%, χ2=7. 946, P=0. 005; and 45. 0% versus 26.0%, χ2 = 112. 723, P<0. 001 ) . The lymph node metastasis ratio of mucinous and signet ring cell adenocarcinoma was 34.9%, significantly higher than 28.5% of the adenocarcinoma (χ2=8.710, P<0.001) The depth of tumor invasion and degree of tumor differentiation were independent factors affecting lymph node metastasis (P=0.001 and P<0.001). Conclusions The lymph node metastasis rate and ratio of AEG are high and influenced by many clinicopathological factors. The patterns of lymph node metastasis are different among different Siewert subtype AEGs.The depth of tumor invasion and differentiation degree are independent factors affecting lymphatic metastasis.

Objective To investigate the clinicopathological characteristics, patterns of lymph node metastasis and the influencing factors in esophageal adenocarcinoma. Methods A total of 201 cases of esophageal adenocarcinoma were selected for this study, including 89 cases of pure adenocarcinoma, 57 cases of adenoacanthoma cell carcinoma, 33 cases of mucoepidermoid carcinoma and 22 cases of adenoid cystic carcinoma. A total of 2026 lymph nodes were dissected with an average of 10 lymph nodes. The rule of lymph node metastasis in patients with esophageal adenocarcinoma was analyzed, and the risk factors for lymph node metastasis were identified. Results Esophageal adenocarcinoma in the middle thoracic esophagus accounted for 50.7% of all patients, and 43.8% in the lower thoracic esophagus. Ninety out of 201 cases (44.8%) had lymph node metastasis. 322 lymph nodes were positive for metastatic adenocarcioma with a metastatic ratio of 15.9% (322/2026).Among the patients with upper?thoracic esophageal carcinoma, 9.1% (1/11) of the cases had lymph node metastasis in the superior mediastinum but no lymph node metastasis was found in the middle mediastinum, lower mediastinal and abdominal lymph nodes. The middle?thoracic esophageal adenocarcinoma showed more extensive lymph node metastasis. Lower mediastinal and abdominal lymph node metastases were common in lower?thoracic esophageal cancer. Multivariate analysis showed that gender, length of lesion, depth of invasion and vascular invasion were independent risk factors for lymph node metastasis in esophageal adenocarcinoma ( P=0. 010, P=0. 006, P=0. 000, P=0. 019, respectively) . Male patients had more lymph node metastasis than female patients ( 49. 1% vs 26. 3%, P=0.011). The rates of lymph node metastasis in the tumor length ≤3 cm group, 3.1?5 cm group and >5 cm group were 20.4%, 42.9% and 65.7%, respectively. Lymphatic metastasis rates in the T1, T2, T3, T4 stage cancers were 7.1%, 36.8%, 38.1% and 69.4%, respectively, (P<0.001). Patients with vascular invasion had a higher rate of lymph node metastasis ( 73. 9%) than the patients without vascular invasion (41.0%) (P=0.003). Conclusions Most of the esophageal adenocarcinoma are distributed in the middle thoracic esophagus, followed by that in the lower thoracic segment. The lymph node metastasis rate, lymph node metastasis ratio and pattern of lymph node metastasis are similar to those of esophageal squamous cell carcinoma. Male, tumor length, depth of invasion and vascular invasion are risk factors of lymph node metastasis for patients with esophageal adenocarcinoma.

Objective To explore the patterns and influencing factors of lymph node metastasis of adenocarcinoma of the esophagogastric junction ( AEG ) . Methods Clinicopathological data of 393 AEG patients who underwent radical resection and lymphadenectomy in the thoracic or abdominal cavity were collected. We analyzed the metastatic patterns of 5 119 excised lymph nodes with an average of 13 nodes per patient according to Siewert classification, and the associations between lymphatic metastasis and clinicopathological factors, such as tumor invasion, differentiation, maximum diameter, or pathological type were analyzed. Results The lymph node metastasis rate and ratio ( LNR) were 70. 0% ( 275/393) and 29.1% (1 492/5 119), respectively. All the Siewert subtypes of AEG mainly metastasize downwards to the abdominal lymph nodes, while also spread upwards to the mediastinal lymph nodes. Among them, the lymph node metastasis rate was highest in Siewert type Ⅰ and lowest in Siewert type Ⅲ AEG. The lymph node metastasis rate and ratio in T1, T2, T3, T4 AEGs were 0%, 29. 4%, 75. 0%, 74. 6% and 0%, 10. 1%, 14.2%, 32.0%,respectively (χ2=35.305,P<0.001 andχ2=134.034,P<0.001) . The lymph node metastasis rate and ratio of the poorly differentiated adenocarcinoma were 36.0% and 79.3%, respectively, significantly higher than 22.1% and 61.7% of the well?differentiated adenocarcinoma (χ2=14.468, P<0.001 and χ2=120.009, P<0.001). The lymph node metastasis rate and ratio of patients with a tumor in maximum diameter≥4 cm were 73.1% and 30.9%, significantly higher than 46.8% and 14.6%, respectively, in the patients with a tumor in maximum diameter of<4 cm (χ2=13.636, P<0.001 andχ2=64.767, P<0.001) . The group of vascular tumor thrombus showed significantly higher lymph node metastasis rate and ratio than those in the group with no vascular tumor thrombus ( 84. 6% versus 67. 1%, χ2=7. 946, P=0. 005; and 45. 0% versus 26.0%, χ2 = 112. 723, P<0. 001 ) . The lymph node metastasis ratio of mucinous and signet ring cell adenocarcinoma was 34.9%, significantly higher than 28.5% of the adenocarcinoma (χ2=8.710, P<0.001) The depth of tumor invasion and degree of tumor differentiation were independent factors affecting lymph node metastasis (P=0.001 and P<0.001). Conclusions The lymph node metastasis rate and ratio of AEG are high and influenced by many clinicopathological factors. The patterns of lymph node metastasis are different among different Siewert subtype AEGs.The depth of tumor invasion and differentiation degree are independent factors affecting lymphatic metastasis.

OBJECTIVETo explore the patterns and influencing factors of lymph node metastasis in limited esophageal small cell carcinoma (PESCC).

METHODSA total of 98 limited stage PESCC patients who underwent surgery were selected for this study. The lymph node metastasis ratio at different sites, depth of invasion, tumor length and other factors were analyzed to assess their influence on lymph node metastasis.

RESULTSAmong the 98 PESCC cases, 46 cases had lymph node metastasis (46.9%). 100 out of 833 lymph nodes had metastasis, with a metastasis ratio of 12.0%. For upper thoracic esophageal small cell carcinomas, lymph node metastasis ratios were 42.9%, 12.5%, 0 and 0 in the superior mediastinum, middle mediastinum, inferior mediastinum and abdominal cavity, respectively. In the middle thoracic PESCCs, the lymph node metastasis ratios were 18.8%, 7.7%, 15.7%, and 15.3%, respectively. In the lower thoracic PESCCs, the lymph node metastasis ratios were 0, 0, 27.3% and 23.5%, respectively. Lymph node metastasis rates in PESCCs at stages T1, T2, T3, T4 were 15.4%, 42.3%, 63.9%, and 80.0%, respectively. The lymph node metastasis ratios in PESCCs at stages T1, T2, T3, T4 were 2.0%, 8.3%, 17.8% and 25.0%, respectively. Lymph node metastasis rate and lymph node metastasis ratio at different T stages were of significant difference (P<0.05 for all). Lymph node metastasis rates in patients with tumor <3 cm, 3-5 cm, and >5 cm were 30.6%, 46.9% and 66.7%, respectively, and lymph node metastasis ratios were 5.4%, 11.0% and 21.1%, respectively. Lymph node metastasis rate and lymph node metastasis ratio in patients with different tumor length had significant differences (P<0.05 for all). Lymph node metastasis ratio was 11.6% in the Chr-A negative and weak positive group, much higher than 4.3% in the Chr-A positive group (P=0.013). There was a tendency that lymph node metastasis ratio of NSE-positive group was higher than that of NSE-negative and weak positive group (P=0.069). The logistic univariate analysis did not find high risk factors of distant lymph node metastasis (all P>0.05). Logistic multivariate analysis found that only depth of invasion was a risk factor of lymph node metastasis in limited PESCC (P=0.002).

CONCLUSIONSEsophagus small cell carcinomas sometimes have early lymph node metastases in many sites and distant range. The middle thoracic PESCCs tend to have extensive metastasis quite common in the upper mediastinal lymph nodes. Lower mediastinal and abdominal lymph node metastases are often seen in lower thoracic PESCCs. The depth of invasion and tumor length are main factors influencing mediastinal lymph node metastasis. The depth of invasion is an independent risk factor for lymph node metastasis.

Abdominal Cavity ; Carcinoma, Small Cell ; pathology ; secondary ; Esophageal Neoplasms ; pathology ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Mediastinum ; Multivariate Analysis ; Neoplasm Invasiveness ; Risk Factors

Background and purpose:Differentiation of tumor tissue is an important factor on determining the prognosis of gastric cancer. This study aimed to investigate the expression levels and clinical signiifcance of gender determining region Y-box 2 (SOX2) gene and octamer binding factor 4 (OCT4) gene in gastric cancer tissues varying different differentiation degrees. Methods: Sixty cases with gastric cancer were recruited in this study. The gastric cancer tissues and corresponding normal mucosa of the 60 cases were obtained. The mRNA and protein level of SOX2, OCT4 gene are evaluated by the quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry, respectively. The relationship between the expression levels of SOX2, OCT4 gene and clinical pathological parameters were also analyzed in this study. Results:The expression of SOX2 in both mRNA and protein levels had no signiifcant difference between the well-differentiated gastric cancer tissues and normal gastric mucosa (mRNA levels:t=0.1033, P>0.05;protein levels:t=0.116, P>0.05). However, both the mRNA and protein expression of SOX2 in patients with well-differentiated gastric cancer tissues were signiifcant higher than not only in patients with moderately differentiated gastric carcinoma (mRNA levels: t=12.48, P<0.05; protein levels: t=22.78, P<0.05) but also in patients with than poorly differentiated gastric carcinoma (mRNA levels:t=17.56, P<0.05;protein levels:t=30.00, P<0.05). In contrast to SOX2, both the mRNA and protein expression of OCT4 in patients with well-differentiated gastric cancer tissues were signiifcant lower than not only in patients with moderately differentiated gastric carcinoma (mRNA levels:t=13.23, P<0.05; protein levels: t=25.56, P<0.05) but also in patients with poorly differentiated gastric carcinoma (mRNA levels: t=12.10, P<0.05; protein levels: t=69.48, P<0.05). There was no significance of OCT4 mRNA and protein expression between the well-differentiated gastric cancer tissues and normal gastric mucosa (mRNA levels:t=2.436, P>0.05;protein levels:t=1.064, P>0.05). Immunohistochemical study demonstrated that the positive rate of SOX2 in patients with well-differentiated gastric cancer tissues (10/21) were higher than in patients with not only moderately differentiated gastric carcinoma (7/20) but also poorly differentiated gastric carcinoma (2/19, P<0.05), while the positive rate of OCT4 in cases with well-differentiated gastric cancer tissues (2/21) were lower than in cases with not only moderately differentiated gastric carcinoma (6/20) but also the poorly differentiated gastric carcinoma (12/19, P<0.05). There was no correlation between the expression of SOX2, OCT4 in gastric cancer and gender or age (P>0.05). Nevertheless, the expression of SOX2, OCT4 were positive or negative correlated with the pathological staging, the degree of inifltration and lymph node metastasis (P<0.05). Conclusion:Decreased SOX2 expression and increased expression level of OCT4 can promote the formation, development and invasion of gastric cancer and they may become biomarkers or the diagnosis, treatment and prognosis evaluation in gastric carcinoma.