[Advances of pathological diagnosis and molecular pathology of lung neuroendocrine neoplasms].

The pathological classification and diagnostic criteria for lung neuroendocrine neoplasms (NENs) in the 2021 World Health Organization (WHO) lung tumor classification are similar to the prior classifications. However, the advances on the molecular studies of lung NENs have shown that both small cell lung carcinoma and large cell neuroendocrine carcinoma are highly heterogeneous tumors with neuroendocrine characteristics and can be subclassified based on the features of genomics or transcriptomics, which are valuable in the diagnosis of lung NENs subtypes and patient treatment. In addition, it is necessary to interpret emerging concepts such as "lung neuroendocrine tumor G3" and "histological transformation" from pathological perspectives, as well as to know the novel neuroendocrine biomarkers such as INSM1 and POU2F3. This article summarized the diagnostic changes and the advances of molecular pathology of lung NENs based on the latest WHO classification and molecular research.

[Correlation of MYB/NFIB gene fusion with the grade and prognosis of head and neck adenoid cystic carcinoma and the concordance of two detection methods].

Objective: To explore the correlation between MYB/NFIB gene fusion and clinicopathological features such as tumor grade and prognosis of head and neck adenoid cystic carcinoma (ACC), and to assess the concordant rate of fluorescent in situ hybridization (FISH) with MYB and NFIB immunohistochemistry. Methods: FISH detection of MYB/NFIB gene fusion was performed on 48 head and neck ACC cases and 15 non-ACC salivary gland tumors at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China during April 2014 and January 2020. ACC cases were divided into grade Ⅰ-Ⅱ, grade Ⅲ and high-grade transformation, according to pathological grading criteria. Prognosis, FISH results and other clinicopathological characteristics were analyzed. MYB and NFIB immunohistochemistry was performed on the 48 ACC and 15 non-ACC cases. The diagnostic accuracy of FISH and immunohistochemistry was compared. Results: FISH detected MYB/NFIB gene fusion in 41.7% (20/48) of the ACC. Its positive rate was inversely correlated with higher pathological grades (P=0.036). The higher histological grade was linked to worse progression-free survival (P=0.024), whereas there was no correlation between the status of gene fusion detected by FISH and progression-free survival (P=0.536). FISH didnot detect MYB/NFIB gene fusion in 15 non-ACC salivary gland tumors The specificity of diagnosing ACC is 100% for both FISH detection of gene fusion and immunohistochemical detection of MYB expression. However, the sensitivity for both methods was only about 41.7%, respectively. By combining FISH and MYB immunohistochemistry, the sensitivity for diagnosing ACC was increased to 66.7%. Conclusions: MYB/NFIB gene fusion has a lower detection rate in grade Ⅲ ACC and high-grade transformation ACC. Meanwhile gene fusion status is not correlated with prognosis. The sensitivity for diagnosing ACC can be improved by combining FISH and MYB immunohistochemistry.

[Diagnostic value of contrast-enhanced ultrasound in hepatic epithelioid hemangioendothelioma].

Objective: To investigate the features of contrast-enhanced ultrasound (CEUS) in hepatic epithelioid hemangioendothelioma (HEHE) in order to improve the preoperative diagnosis rate. Methods: CEUS images of 32 pathologically-proven cases of hepatic epithelioid hemangioendothelioma from January 2004 to August 2021 were collected. Lesions were analyzed to observe the features of enhancement mode, enhancement intensity, and distinct enhancement phases. Results: Among the 32 cases, one had a solitary lesion, 29 had multiple lesions, and two had diffuse-type lesions. Contrast-enhanced ultrasound revealed a total of 42 lesions in 32 cases. In terms of arterial phase enhancement, 18 lesions had overall enhancement, six lesions had uneven dendritic enhancement, 16 lesions had rim-like enhancement, and two lesions had just slight peripheral spot enhancement around the lesions. Among the three cases, there were multiple lesions that had overall enhancement and ring enhancement. In terms of the enhancement phase, 20 lesions showed "fast progression", 20 lesions showed "same progression", and two lesions showed "slow progression". During the late arterial or early portal venous phases with rapid washout, all lesions manifested as hypoechoic. With peaked enhanced intensity, 11 lesions had a lower enhancement intensity than the surrounding normal liver parenchyma; 11 lesions had the same enhancement degree as the surrounding normal liver parenchyma; and 20 lesions had a higher enhancement degree than the surrounding normal liver parenchyma. All 16 ring-enhancing lesions had marked hyperenhancement. In the typical enhancing lesions, four showed hyperenhancement, five showed low enhancement, and nine showed isoenhancement. In the dendrite-enhancing lesions, there were two isoenhancing and four hypoenhancing. Contrast-enhanced ultrasound delineated the boundaries of all lesions more clearly than two-dimensional ultrasound. Conclusion: Contrast-enhanced ultrasound has certain value in the diagnosis of hepatic epithelioid hemangioendothelioma.

[Study on the recurrence pattern of rectal cancer patients undergoing radical surgery after neoadjuvant chemoradiotherapy].

Objective: To analyze the recurrence pattern of rectal cancer patients with radical surgery after neoadjuvant chemoradiotherapy. Methods: The clinicopathological characteristics and follow-up information of rectal cancer patients with radical surgery after neoadjuvant chemoradiotherapy in the Cancer Hospital of the Chinese Academy of Medical Sciences from June 2004 to December 2017 were retrospectively collected. The recurrence pattern including the time and site was investigated. Results: The age of 537 patients was (55.5±11.7) years, of whom 361 were male (67.2%). The median follow-up time [M(Q1,Q3)] was 77.9 (64.5, 95.6) months. Moreover, 30.7% (165/537) of patients had distant metastasis or local recurrence; 26.8% (144/537) of patients had distant metastasis; 5.6% (30/537) of patients had local recurrence; 1.7% (9/537) of patients had both distant metastasis and local recurrence. In all the recurrent patients, 23.6% (39/165) were in the first year after surgery, followed by 27.3% (45/165) in the second year, 17.0% (28/165) in the third year, and 15.8% (26/165) after five years. According to the risk curve drawn by the life table, the highest metastasis risk of patients occurred in the second year after surgery, and the metastasis risk peak occurred again after more than five years. The lung was the most common metastatic organ, accounting for 47.9% (69/144), followed by the liver (18.8%, 27/144). The ratios of the recurrent patients in each ypTNM stage were 9.5% (8/84), 12.0% (12/100), 26.5% (41/155), 52.5% (104/198), respectively. The proportion of recurrent patients in tumor regression grade (TRG) 1-2 and TRG 3-5 patients were 19.2% (38/198) and 37.5% (127/339), respectively. Conclusions: The recurrence pattern of patients undergoing radical surgery after neoadjuvant chemoradiotherapy is mainly distant metastasis. The lung is the primary metastatic organ. The risk of distant metastasis and local recurrence is high in the first three years after surgery, and there is still high risk of recurrence after five years. For patients with ypTNM stage 2, 3 and TRG3-5, the postoperative adjuvant chemotherapy and long-term follow-up should be strengthened.

The composition of the intestinal microbiota after allogeneic haematopoietic stem cell transplantation and its association with graft versus host disease as assessed by 16Sribosomal ribonucleic acid.

To observe the evolution of the intestinal microbiota in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and discuss the relationship between the intestinal microbiota and graft-versus-host disease (GVHD). In this study, 11 patients who underwent allo-HSCT in the Aerospace Central Hospital from January 2021 to October 2021 were selected, along with 11 donors. Fecal specimens were collected 7 times: at admission, after pre-treatment, and every 3 weeks after transplantation from patients and once from donors. The composition of the intestinal microbiota and its association with GVHD after allogeneic hematopoietic stem cell transplantation were analyzed by 16S rRNA sequencing. Of the 11 patients, 5 developed GVHD, and 6 did not. The diversity of the intestinal microbiota among GVHD patients first increased and then decreased after transplantation, while that among non-GVHD patients first increased and then tended to be stable. The diversity of the intestinal microbiota among GVHD patients was lower than that among non-GVHD patients before pre-treatment and after transplantation. The taxa diversity of the intestinal microbiota in the non-GVHD group was better than that in the GVHD group before allo-HSCT, and the difference was statistically significant (P<0.05 for OTUs and CHAO1 index). The taxa abundance of Enterococcaceae 2.16% (2.13%, 2.22%) before allo-HSCT was significantly higher than that in the non-GVHD group 1.33% (0.27%, 1.52%), and the difference was statistically significant (P=0.004). There was no significant difference between the GVHD group and the non-GVHD group in the diversity of the intestinal microbiota of donors (P<0.05). The characteristics of the intestinal microbiota in the final sample of patients in the GVHD group were similar to the preoperative structure of the intestinal microbiota. In conclusion: The decrease in the diversity of the intestinal microbiota after HSCT may be a risk factor for the occurrence of GVHD. The presence of Enterococcaceae in the intestinal microbiota may be associated with an increased risk of developing GVHD. The intestinal microbiota reconstitute to be close to the intestinal microbiota composition of the donors in the non-GVHD group.

[A long-term follow-up study on recurrence and benefit of standardized postoperative chemotherapy of rectal cancer patients with complete pathological response after neoadjuvant chemoradiotherapy].

Objective: To analyze the clinicopathological factors affecting long-term disease-free survival and the characteristics of local recurrence or distance metastasis of rectal cancer patients with complete pathological response after neoadjuvant chemoradiotherapy. Methods: The clinicopathological data and follow-up information of patients with a complete pathological response of rectal cancer after neoadjuvant chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from June 2004 to December 2019 were retrospectively collected. The clinicopathological factors affecting the long-term disease-free survival of patients were analyzed to build a prediction model of local recurrence and distant metastasis and to evaluate the benefits of postoperative chemotherapy. Results: The age of 108 patients was(56.3±11.6) years, of which 68 were males (63.0%); The median follow-up time was 79.9 (61.8, 112.6) months. There were 12 patients (11.1%) who had a local recurrence or distant metastasis. The 5-year disease-free survival rate was 91.1% with 9 patients who experienced recurrence. Multivariate Cox proportional hazards regression analysis showed that the maximum diameter of the residual tumor or scar (HR=8.41, 95%CI: 1.08-65.22, P=0.042) and the distance from the lower edge of the tumor to the anal margin before treatment (HR=4.54, 95%CI: 1.23-16.81, P=0.023) were independent risk factors affecting the prognosis. The prognosis of patients was stratified based on relevant factors. The 5-year cumulative disease-free survival rate of those patients receiving postoperative standardized chemotherapy was 92.0%, while for patients who did not receive or complete standardized chemotherapy, the 5-year cumulative disease-free survival rate was 82.3%. Conclusions: The maximum diameter of the residual tumor or scar and the distance from the lower edge of the tumor to the anal margin before treatment were independent risk factors affecting the prognosis of patients with a complete pathological response. Patients with independent risk factors could benefit from the standardized postoperative chemotherapy.

[Analysis of recurrent factors and therapeutic effect after laparoscopic inguinal hernia repair].

Objective: To analyze the recurrence factors and reoperation effect of laparoscopic inguinal hernia repair. Methods: A total of 41 patients with recurrence after laparoscopic repair of the inguinal hernia admitted to the Department of Hernia and Abdominal Wall Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2017 to December 2021 were retrospectively analyzed. All patients were males, aging (62±7) years (range: 51 to 75 years). The recurrence intervals were 3 days to 7 years postoperatively. The surgical methods, causes of recurrence, and treatment outcomes of the patients were analyzed. Fisher exact probability method is used to compare the rates. Results: Among all cases, the primary surgical procedures included transabdominal preperitoneal herniorrhaphy (TAPP) in 31 cases and total extraperitoneal herniorrhaphy in 10 cases. The reoperative procedures included the TAPP of 11 cases and the Lichtenstein procedure of 30 cases. The factors of recurrent cases in all patients could be divided into 4 categories, including insufficient mesh coverage in 23 cases, mesh curling in 9 cases, mesh contractuture in 7 cases, and improper mesh fixation in 2 cases. Recurrence, infection, chronic pain, foreign body sensation didn't occur in the followed period of(M(IQR)) 18(24) months(range: 12 to 50 months). There was no statistical difference in the incidence of postoperative seroma between the TAPP and Lichtenstein procedure (3/11 vs. 20.0% (6/30), P=0.68). Conclusions: Postoperative recurrence of laparoscopic inguinal hernia is mostly caused by the lack of mesh coverage. Due to the emphasis on standardized surgical operation, a good outcome could be achieved through reoperation by the TAPP or Lichtenstein procedure.

[The analgesic efficacy and safety of non-steroidal anti-inflammatory drugs combined with medial canthus peribulbar block for postoperative pain in patients with thyroid-associated ophthalmopathy after orbital decompression].

Objective: To explore the analgesic efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) combined with medial canthus peribulbar block for postoperative pain in patients with thyroid-associated ophthalmopathy (TAO) after orbital decompression. Methods: This study was a single-center, single-blind, randomized controlled study. From June 2020 to December 2020, sixty TAO patients in Zhongshan Ophthalmic center, Sun Yat-sen University who were allocated to receive orbital decompression under general anesthesia, were randomly and equally divided into two groups (n=30): the control group (group C) and the medial canthus peribulbar block group (group PB). All patients received intravenous infusion of flurbiprofen axetil 50 mg at 15 min before the end of surgery. In PB group, patients received peribulbar block via caruncular approach for postoperative pain management upon completion of wound closure, while patients in group C did not receive the peribulbar block. If patient sufferred significant postoperative pain (NRS score≥4), Ketorolac 10 mg would be prescribed as analgesic rescue. Postoperative NRS pain scores were recorded at 2, 4, 8, 24, 48 h after the surgery. The usage of Ketorolac during 0-24 h and 24-48 h postoperatively were also recorded. Postoperative complications during the hospital stay were recorded. Severity of orbital swelling would also be evaluated at 24 h after surgery. Results: The NRS pain scores [M(Q1, Q3)] in group PB were 2.50(2.00, 3.00)and 2.00(1.75, 3.00), which were both significantly lower than those in group C of 4.50(3.00,5.00), 3.00(2.00,4.25)at 2 h, 4 h after surgery respectively(P=0.001,0.045). During the first 24 h, the usage rate of Ketorolac in group C was 40%(12/30), which was higher than that in the group PB (13.3%, 4/30) with statistical significance (P=0.041). There was no significant difference in the incidences of postoperative nausea, vomiting, dizziness during the first 48 h, as well as the moderate to severe intensity of orbital swelling at 24 h after surgery (all P>0.05). There were no obvious complications of medial canthus peribulbar block in group PB. Conclusions: NSAIDs combined with medial canthus peribulbar block can provide satisfactory analgesia for TAO patients after orbital decompression, which is safe with little complications, and is beneficial to enhanced recovery after surgery.

[Analysis of clinical features and etiological diagnostic indices of reproductive age women with hyperandrogenism].

Objective: To investigate the clinical features and the value of different diagnostic indices for etiology in reproductive age women with hyperandrogenism. Methods: The medical records of 96 reproductive age women with hyperandrogenism in the multi-disciplinary team of Peking University First Hospital from January 2020 to April 2021 were collected. The patients were divided into four groups based on final diagnosis: congenital adrenal hyperplasia (CAH) (n=8), polycystic ovary syndrome (PCOS) (n=67), idiopathic hyperandrogenism (n=13) and other specific diseases (n=8), respectively. The indices related to androgens in different groups were compared, and then their efficiency for diagnosis of CAH and PCOS were analyzed with receiver operator characteristic curve (ROC curve). Results: A total of 96 patients with hyperandrogenism were recruited, with the age of 19-45 (29±6) years old. Overall, 4.2% (4/96) of the patients were with single clinical hyperandrogenism, 56.3% (54/96) were with single laboratory hyperandrogenaemia and 39.6% (38/96) were with both. The breakdown into laboratory hyperandrogenaemia subtypes was as follows: only T elevation 22.8% (21/92), only A2 elevation 7.6% (7/92), none DHEAS elevation, only FAI elevation 5.4% (5/92) and elevation of more than one of the androgen indices mentioned above accounted for 64.1% (59/92). In the reasons of consultation, simple irregular menstruation (36.0%, 32/89) or accompanied by clinical hyperandrogenism with or without infertility (36.0%, 32/89) were the most common. As for primary visiting departments, Obstetrics and Gynecology accounted for 53.2% (51/96), and then Endocrinology as 39.5% (38/96). The 17-OHP level of CAH, PCOS and idiopathic hyperandrogenism group was 20.0 (8.2, 33.1), 1.1 (0.8, 1.4), 0.9 (0.8, 1.3) ng/ml, respectively. The androstenedione level in these groups was 6.3 (4.6, 8.7), 3.8 (2.9, 4.8) and 3.2 (2.7, 3.7) ng/ml, respectively. The 17-OHP and androstenedione levels of CAH group were significantly higher than that in PCOS or idiopathic hyperandrogenism group (all P<0.05). The ratio of LH and FSH in these three groups was 0.8(0.5, 1.0), 1.3(0.6, 1.9) and 0.6(0.3, 0.7), respectively. The ratio of LH and FSH was significantly higher in PCOS than that in idiopathic hyperandrogenism group (P=0.024), but yet there was no significant difference compared with CAH group (P>0.05). The AUC of ROC curve of 17-OHP for CAH diagnosis was 0.94, followed by androstenedione 0.83, whereas LH/FSH for PCOS diagnosis was only 0.63. Conclusions: Among the reasons of consultation in reproductive age women who visited our multi-disciplinary team for female hyperandrogenism, simple irregular menstruation or accompanied by clinical hyperandrogenism with or without infertility are the most common. PCOS accounts for the majority of different androgen excess disorders. 17-OHP is the most valuable parameter for the diagnosis of CAH and secondly androstenedione.

[Long-term conditional disease-free survival for rectal cancer patients underwent neoadjuvant chemoradiotherapy].

Objective: To explore the application value of the conditional disease-free survival (cDFS) analysis in predicting prognosis of stage-specific rectal cancer patients underwent neoadjuvant chemoradiotherapy (nCRT). Methods: Clinicopathologic data of 436 patients with rectal cancer received nCRT and radical operation in Cancer Hospital, Chinese Academy of Medical Sciences between January 2004 and December 2016 were retrospectively reviewed. With reference to conditional probability, the 3-year cDFS of patients at different ypTNM stage after completion of nCRT was estimated using the Kaplan-Meier method. Results: There were 66 patients of ypTNM stage 0 (pathological complete response), 87 patients of ypTNM stage Ⅰ, 135 patients of ypTNM stage Ⅱ and 148 patients of ypTNM stage Ⅲ. The 3-year accumulated DFS of patients with ypTNM stage 0, ypTNM stage Ⅰ, ypTNM stage Ⅱ, and ypTNM stage Ⅲ were 97.0%, 93.1%, 85.2%, and 64.2%, respectively. On the condition of postoperactive disease-free survival for 1 year, 2 years, 3 years, 4 years, and 5 years, the corresponding 3-year cDFS of patients at ypTNM stage 0 were 97.0%, 95.5%, 96.9%, 98.4%, 100.0%, respectively. The corresponding 3-year cDFS of patients at ypTNM Ⅲ were 68.2%, 79.3%, 86.3%, 92.1%, 96.4%, respectively. The more advanced ypTNM staging resulted in the more improvement of 3-year cDFS being acquired. Conclusion: cDFS is a better method to reflect the dynamic changes of the prognosis of rectal cancer patients with nCRT in different ypTNM stage, and it is useful to guide the clinicians to assess the prognosis and propose appropriate surveillance.

[The risk factors for regional lymph node metastasis of mismatch repair deficient colorectal cancer].

Objective: To explore the risk factors for regional lymph node (RLN) metastasis in colorectal cancer patients with mismatch repair deficiency (dMMR). Methods: The data of 357 dMMR colorectal cancer patients who underwent surgery in National Cancer Center from January 2012 to December 2016 was retrospectively analyzed. Univariate and multivariate analysis were used to identify the risk factors for RLN metastasis. Results: Among the 357 patients, 204 were male and 153 were female, 61.6% (220/357) lesion located in right half colon, while the other 16.2% (58/357) located in rectum. Univariate analysis showed that tumor size, differentiation, lymphovascular invasion, tumor deposit, postoperative pathologic T stage (pT), the number of negative lymph nodes and the expression of the MSH6 protein were significantly associated with RLN metastasis (P<0.05). All of the patients with well differentiation tumors (15 patients) or staged pT1 (13 patients) had no RLN metastasis. Multivariate analysis showed that tumor differentiation (OR=2.582, 95%CI=1.567-4.274, P<0.001), pT (OR=3.778, 95%CI=1.448-12.960, P=0.015) and the expression of MSH6 protein (OR=2.188, 95%CI=1.159-4.401, P=0.021) were independent risk factors for RLN metastasis. Conclusions: The postoperative pT stage, tumor differentiation and the expression of MSH6 protein are independent risk factors for RLN metastasis of dMMR colorectal cancer. Preoperative assessment of these factors may further improve the accuracy of predicting the risk of RLN metastasis.

[Clinicopathological and prognostic features of young onset patients with middle-low rectal cancer received neoadjuvant chemoradiotherapy].

Objective: To explore the clinicopathological and prognostic features of young onset patients with middle-low rectal cancer who received neoadjuvant chemoradiotherapy (NCRT). Methods: After NCRT, a total of 441 patients with primary middle-low rectal cancer treated with radical surgery at the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from January 2004 to December 2016 were included. According to the age of disease onset, the patients were divided into the young group (51cases) and the middle-old group (390 cases), and the clinicopathological characteristics and survival of these patients were analyzed. Results: In the young group, 68.6% of patients received radical surgery within 7 weeks after NCRT, which was higher than 52.8% in the middle-old group (P=0.047). The stage ypTNM Ⅲ in the young group was 51.0%, higher than 34.1% in the middle-old group (P=0.027). The stage ypN+ in the young group was 51.0%, higher than 34.1% in the middle-old group (P=0.047), The incidence of disease progression in the young group was 39.2%, higher than 25.1% in the middle-old group (P=0.049). The incidence of distant metastasis in the young group was 35.3%, higher than 21.5% in the middle-old group(P=0.044). Most cases of disease progression occurred in the first 3 years after surgery for the young group, especially in the second year after surgery, the incidence of disease progression in the young group was 55.0%, higher than 26.5% in middle-old group (P=0.025). The 3-year and 5-year disease-free survival (DFS) rates for the young group were 63.7% and 58.2%, lower than 81.0% and 74.3% in the middle-old group (P=0.016), respectively. The 3-year and 5-year overall survival in the middle-old group (OS) rates for the young group were 85.4% and 69.2%, lower than 93.6% and 84.1% in the middle-old group (P=0.033), respectively. The multivariate analysis showed that, response of primary tumor (HR=4.804, 95% CI: 1.360-16.973) and total number of dissected lymph nodes (HR=4.336, 95% CI: 1.739-10.809) in the young group were independent prognostic factors related to DFS. The total dissected number of lymph nodes(HR=3.295, 95% CI: 1.076-10.091)was an independent prognostic factor related to OS. In the middle-old group, response of primary tumor (HR=2.626, 95% CI: 1.354-5.091), ypTNM stage (ypTNM Ⅲ: HR=5.837, 95% CI: 2.968-11.479) and tumor location distance from the anal verge (HR=0.500, 95% CI: 0.308-0.812) were independent prognostic factors related to DFS. Lymphovascular invasion (HR=0.500, 95% CI: 0.308-0.812) and ypTNM stage (ypTNM Ⅲ: HR=16.322, 95% CI: 5.049-52.771) were independent prognostic factors related to OS. Conclusions: Young onset rectal cancer patients are associated with shorter operation time interval, advanced pathological stage and poorer prognosis. More intensive adjuvant treatment and post-treatment surveillance should be conducted to young onset rectal cancer with NCRT.

[Clinicopathological characteristics and prognostic analysis of patients with pathological complete response and near complete response after neoadjuvant treatment of rectal cancer].

Objective: To investigate the clinicopathological characteristics and prognosis of rectal cancer patients with pathological complete response and near complete response after neoadjuvant therapy. Methods: The clinicopathological data of patients who underwent neoadjuvant chemoradiotherapy plus radical surgery of rectal cancer in the Cancer Hospital of Chinese Academy of Medical Sciences from January 2004 to December 2016 were retrospectively collected. The clinicopathological characteristics and prognostic factor of patients with pathological complete response and near complete response were analyzed. Results: The clinical data of 142 patients were collected. There were 93 males and 49 females, aged from 24 to 81 years. The median disease-free survival was 53.9 months and the median overall survival was 55.0 months. Univariate analysis showed that the maximum diameter of scar or lesion, the status of lymph node metastasis and the distance between the lower edge of tumor and anal edge were associated with disease-free survival time; the maximum diameter of scar or lesion and the status of lymph node metastasis were associated with overall survival time. Multivariate Cox proportional hazards regression analysis showed that patients with scar or lesion diameter>3 cm (HR=4.406,95%CI:1.619-12.006), positive lymph node metastasis status (HR=4.102,95%CI:1.461-11.513) and tumor lower margin to anal margin distance ≤4 cm (HR=18.171,95%CI:2.357-140.073) had shorter disease-free survival time.The patients with scar or lesion diameter>3 cm (HR=8.573,95%CI:1.630-45.099) and lymph node metastasis status (HR=4.721, 95%CI:1.068-20.860) had shorter overall survival time. Conclusions: The overall prognosis of patients with pathological complete response or near complete response after neoadjuvant therapy for rectal cancer is better. The distance between the lower margin of the tumor and the anal edge, the status of lymph node metastasis and the maximum diameter of scars or lesion were the related factors affecting the prognosis of patients with rectal cancer.

[Clinical and imaging characteristics of patients with primary cardiac angiosarcoma].

Objective: To investigate the clinical, cardiac imaging characteristics and prognosis of patients with primary cardiac angiosarcoma. Methods: The clinical data of 14 patients hospitalized with primary cardiac angiosarcoma from January 2001 to December 2017 in Peking Union Medical College Hospital were collected and analyzed. Metastatic cardiac angiosarcoma was not included in this study. Patients were followed up post discharge per telephone call or clinical visit. Results: Of the 14 patients, 8 were males and 6 were females, average age was 48 years. The main clinical symptoms were shortness of breath (8/14), hemoptysis (6/14), fever (5/14), chest pain (4/14) and cough (3/14). Imaging examinations showed that the tumors of 8 patients were located in the right heart and 6 in the pericardial cavity. Tumors in the right heart often infiltrate the atrial wall and cause pericardial effusion (7/8). Tumors in the pericardium were characterized by recurrent bloody pericardial effusion (6/6), prone to progressive constrictive pericarditis (3/6), pericardial fluid cytology was often negative (6/6). MRI showed heterogeneous high signal intensity (cauliflower aspect) on T2-weighted image and heterogeneous enhancement with a"sunray" aspect at the perfusion study. At the time of diagnosis, 8 patients developed lung or adrenal metastasis (8/14). The median survival was only 305 days. Conclusions: Primary cardiac angiosarcoma is a rare disease with non-specific clinical manifestation and poor prognosis. Imaging examinations may help diagnosis. The high invasiveness and the easy-to-metastasis feature of the tumor contribute to the poor prognosis of cardiac angiosarcoma.

Antitumor effects of apoptin expressed by the dual cancer-specific oncolytic adenovirus - a review.

Apoptin is a small molecular weight protein derived from chicken anemia virus, which can induce the apoptosis of transformed cells and tumor cells and leave primary and nontransformed cells unharmed. Apoptin's cell localization depends on its own phosphorylation state and cell type. In tumor cells, phosphorylated apoptin enters the nucleus and induces apoptosis. While, in normal cells apoptin mainly exists in the cytoplasm. Apoptin, as a disordered protein in cells, interacts with many proteins in cell signal pathways to induce apoptosis of tumor cells. The specific mechanism of apoptosis induced by apoptin has not been completely elucidated. Therefore, apoptin has become a potential anticancer agent. This review summarizes the research results of apoptin in our laboratory and reveals the specific antitumor mechanism of apoptin expressed by oncolytic virus vector on a variety of tumor cells and mouse models.

[Predictive value of two-dimentional shear wave elastography in posthepatoectomy liver failure].

Objective: To investigate the value of two-dimensional shear wave elastography (2D SWE) combined with clinical biochemical data in predicting posthepatoectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). Methods: A total of 274 HCC patients who underwent hepatectomy in Zhongshan Hospital Fudan University from January 2015 to January 2016 were retrospectively collected, including 235 males and 39 females, age 19-80 (56±11) years. All patients were confirmed to be HCC by postoperative pathology. The preoperative 2D SWE examination, laboratory examination results and intraoperative indicators were analyzed. According to the occurrence of PHLF after surgery, single factor analysis and multiple logistic regression analysis were performed on the above indicators to obtain a binary logistic regression model, and evaluate the diagnostic effect of the model on PHLF. In addition, 103 HCC patients from October 2019 to January 2020 were retrospectively collected as an external validation set, including 89 males and 14 females, age 23-80 (55±11) years old. Results: The liver stiffness measurement (LSM) obtained from 2D SWE, INR and Laminin (LN) were independent predictors of PHLF. The formula of prediction model PM=-15.451+0.095×LSM+11.7×INR+0.012×LN was obtained by combining above three factors. The area under the curve (AUC) of PHLF was 0.82, which was higher than that of end-stage liver disease model (MELD) score and Child-Pugh grading diagnosis of PHLF. The AUC of PHLF predicted by PM in the external validation group was 0.81. Conclusion: 2D SWE is helpful for clinicians to evaluate liver reserve function preoperatively and to predict the occurrence of PHLF in patients with HCC.

[Preliminary study of the clinical value of colposcopy in diagnosing vagina invasion in cervical cancer].

Objective: To explore the preliminary clinical values of colposcopy in the diagnosis of vaginal invasion in cervical cancer. Methods: A retrospective review of the clinical records of patients (31 cases) with cervical cancer treated in Xuzhou Cancer Hospital from April 2015 to August 2019. For those with early-stage cervical cancer and the vagina invasion being difficult to be determined, those with advanced cervical cancer and the scope of vaginal invasion being difficult to be judged, and those with obvious vaginal tumor and underexposed cervix or inconspicuous cervical lesion and the primary location needing to be identified, colposcopy-guided vaginal and cervix biopsy were performed before treatment. Results: (1) Image characteristics of colposcopy and pathological diagnosis: among 31 cases, 30 of them had the similar images of vagina and cervix. The images were dense acetowhite and (or) thick mosaic, coarse punctate and atypical vessels. Lugol's staining was uniformly bright yellow or brown. Pathological biopsy of vaginal wall: 27 cases were metastatic carcinoma, 3 cases were vaginal intraepithelial neoplasia (VaIN) Ⅱ-Ⅲ. One case showed dense acetowhite epithelium and atypical vessels image in cervix and thin acetowhite epithelium in upper 1/3 vagina which disappeared in two minutes; the results of vaginal biopsy was chronic inflammation. (2) Vaginal invasion diagnosed by colposcopy: among 31 cases, 14 of them without invasion of uterine side, vaginal invasion was judged as followed by colposcopy, being consistent with biopsy: 1 case of chronic vaginitis, 2 cases VaINⅡ, 1 case VaINⅢ, 6 cases upper 1/3 vagina invasion, 4 cases lower 1/3 vagina invasion. Among 10 cases with invasion of uterine side, vaginal invasion were identified by colposcopy, being consistent with biopsy: 4 cases upper 1/3 vagina invasion and 6 cases upper 1/2 vagina invasion. Five cases who had clinical diagnosis of vaginal cancer were diagnosed as cervical cancer with vaginal invasion by colposcopy, being consistent with biopsy. Two cases with no obvious lesions of cervix and vagina were diagnosed as cervical cancer with vaginal invasion by colposcopy, being consistent with cervical and vaginal biopsy: 1 case with stage Ⅳ (transfer to the left supraclavicular lymph node) and 1 case with stage Ⅱ a1. Conclusions: Colposcopy and multi-point biopsy have complementary diagnostic value for the cervical cancer cases that the invasion and scope of vagina are difficult to be determined by physical examination and (or) imaging examination. Thus the range of vaginal resection for patients underwent operation and the lower boundary of pelvic radiation field for those underwent radiotherapy could be fixed, so as to make the treatment much more individualized and humanized; the indications need further discussion.

MiR-491 functions as a tumor suppressor through Wnt3a/ß-catenin signaling in the development of glioma.

OBJECTIVE: Glioma is the most frequent brain tumor that has high invasion and usually disperses to the whole brain through blood and basement membranes. MicroRNA-491 (miR-491) has been reported to have low expression and act as a tumor suppressor in several cancers. The Wnt/ß-catenin signaling is a classic signaling pathway that participated in several biological processes. Our purpose was to detect the molecular mechanism of miR-491 in regulating the growth and metastasis of glioma. MATERIALS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was applied to calculate the mRNA level of miR-491 and target gene. The protein expression of special genes was assessed by Western blot. The proliferation and invasive abilities were measured by the Cell Counting Kit-8 (CCK-8) and transwell assays. The Kaplan-Meier method was conducted to evaluate the association between the expressions of miR-491 with the overall survival of glioma patients. RESULTS: We discovered that miR-491 was lowly expressed in glioma and downregulation of miR-491 predicted poor outcome of glioma patients. Similarly, a high expression of miR-491 suppressed the growth and metastasis in glioma cell line LN229. MiR-491 high expression inhibited the growth of glioma in a mouse xenograft model. Moreover, Wnt3a was a target gene of miR-491 and miR-491 mediated the invasion-mediated epithelial-mesenchymal transition (EMT) by regulating the expression of Wnt3a. Additionally, miR-491 regulated the proliferation through the Wnt/ß-Catenin pathway by targeting Wnt3a. CONCLUSIONS: MiR-491 overexpression inhibited the proliferation through the Wnt3a/ß-catenin pathway and invasion-mediated EMT in glioma. The newly identified miR-491/Wnt3a/ß-catenin axis provides novel insight into the pathogenesis of glioma.

Long noncoding RNA UCA1 regulates proliferation and apoptosis in multiple myeloma by targeting miR-331-3p/IL6R axis for the activation of JAK2/STAT3 pathway.

OBJECTIVE: We attempted to clarify the regulatory mechanism of UCA1/miR-331-3p/IL6R on cell progression in multiple myeloma (MM). PATIENTS AND METHODS: The expression of UCA1, miR-331-3p, and IL6R in tumor tissues and cells was measured by qRT-PCR. Cell Counting Kit-8 (CCK-8) was conducted to detect cell proliferation, and flow cytometry assay was applied to examine cell apoptosis. Protein expression of L6R, p-JAK2, p-STAT3, c-Myc, CyclinD1, Bcl-2, and Bax was detected by Western blot assay. The interaction among miR-331-3p, UCA1, and IL6R was determined by Luciferase reporter system. Murine xenograft assay was performed to confirm the biological function of UCA1 in vivo. RESULTS: The expression of UCA1 and IL6R was up-regulated, while miR-331-3p was down-regulated in MM tumors and cell lines compared with normal tissues and cells. By calculation, miR-331-3p was correlated with UCA1 or IL6R inversely. In addition, UCA1 knockdown suppressed cell proliferation and promoted apoptosis in vitro and in vivo. Luciferase reporter system confirmed the interaction between miR-331-3p and UCA1 or IL6R. More importantly, UCA1 restored miR-331-3p mediated inhibition of proliferation and promotion on apoptosis of MM cells. Consistently, IL6R rescued UCA1 knockdown caused repression on MM cell growth and elevation on apoptosis. Besides, UCA1 facilitated the activation of the JAK2/STAT3 signaling pathway by enhancing IL6R expression via targeting miR-331-3p. CONCLUSIONS: UCA1 accelerates proliferation and suppresses apoptosis in MM by targeting miR-331-3p/IL6R axis to activate JAK2/STAT3 pathway, providing potential targets for the diagnosis and therapy of MM.