Objective: To evaluate the safety and efficacy of anlotinib plus irinotecan in the second-line treatment of patients with metastatic colorectal cancer (mCRC). Methods: This prospective phase 1/2 study was conducted in 2 centers in China (Cancer Hospital of Chinese Academy of Medical Sciences and Jiangsu Province Hospital). We enrolled patients with mCRC whose disease had progressed after first-line systemic therapy and had not previously treated with irinotecan to receive anlotinib plus irinotecan. In the phase 1 of the trial, patients received anlotinib (8 mg, 10 mg or 12 mg, po, 2 weeks on/1 week off) in combination with fixed-dose irinotecan (180 mg/m(2), iv, q2w) to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). In the phase 2, patients were treated with the RP2D of anlotinib and irinotecan. The primary endpoints were MTD and objective response rate (ORR). Results: From May 2018 to January 2020, a total of 31 patients with mCRC were enrolled. Anlotinib was well tolerated in combination with irinotecan with no MTD identified in the phase 1, and the RP2D was 12 mg. Thirty patients were evaluable for efficacy analysis. Eight patients achieved partial response, and 21 had stable disease, 1 had progressive disease. The ORR was 25.8% and the disease control rate was 93.5%. With a median follow-up duration of 29.5 months, the median progression-free survival and overall survival were 6.9 months (95% CI: 3.7, 9.3) and 17.6 months (95% CI: 12.4, not evaluated), respectively. The most common grade 3 treatment-related adverse events (≥10%) were neutropenia (25.8%) and diarrhea (16.1%). There was no treatment-related death. Conclusion: The combination of anlotinib and irinotecan has promising anti-tumor activity in the second-line treatment of mCRC with a manageable safety profile.
Humans ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Colorectal Neoplasms/pathology* ; Indoles/therapeutic use* ; Irinotecan/therapeutic use* ; Prospective Studies

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

OBJECTIVE: To compare the efficacy and safety of complete transperitoneal laparoscopic nephroureterectomy (CTNU) and traditional retroperitoneoscopic nehroureterectomy (TRNU) for the management of upper urinary tract urothelial carcinoma(UTUC). METHODS: We retrospectively collected the clinical data of UTUC patients who underwent CTNU or TRNU surgery from January 2011 to December 2018 in Peking University First Hospital and Fujian Provincial Hospital, and compared the clinical characteristics, perioperative parameters, and follow-up results between the CTNU and TRNU surgeries. RESULTS: Finally, a total of 266 cases were included, with 94 cases in the CTNU group and 172 cases in the TRNU group. The proportion of left side lesions was bigger in TRNU group when compared with CTNU group (P<0.05). No significant differences were observed in clinical characteristics, such as age, gender, body mass index (BMI), American society of anesthesiologists score (ASA score) and tumor laterality. All surgery procedures were completed. The vascular resparing was performed by reason that left arteria renalis was injured accidently during surgical operation in one case of TRNU group. No serious complications were observed in both CTNU and TRNU groups. In CTNU group, operating time was (202.9±76.7) min, estimated blood loss was (68.4±73.3) mL, drainage duration was (3.9±1.5) d, drainage volume was (181.7±251.5) mL, and postoperative hospital stay was (7.8±4.1) d. In TRNU group, operating time was (203.5±68.7) min, estimated blood loss was (130.2±252.1) mL, drainage duration was (4.3 ±1.6) d, drainage volume was (179.1±167.5) mL, and postoperative hospital stay was (8.2±3.7) d. The estimated blood loss in CTNU group was significantly less than that in TRNU group (P=0.005).The median follow-up time was 39 months (range: 1-88 months). The 5-year overall survival rate (OS), cancer specific survival rate (CSS), intra-vesical recurrence free survival rate (IvRFS), disease free survival rate (DFS) of CTNU group was 75.6%, 86.9%, 73.8%, 57.5%, respectively. The OS, CSS, IvRFS and DFS of TRNU group was 66.3%, 83.5%, 75.9%, 58.6%, respectively.No significant differences were observed in the OS, CSS, IvRFS and DFS between the CTNU and TRNU groups. CONCLUSION CTNU technique is a safe and effective surgical option, and further prospective randomized controlled trial is needed for further evaluation.
Carcinoma, Transitional Cell ; Humans ; Nephrectomy ; Nephroureterectomy ; Retrospective Studies ; Treatment Outcome ; Urologic Neoplasms

Several studies have demonstrated an association between physical activity and telomere length; however, the association remains inconsistent. A cross-sectional study consisting of 588 participants (375 females, median age of 33.8 years) was carried out to investigate the association between telomere length and physical activity in a general population from North China. The results show that relative telomere length is not significantly different in participants in the northern Chinese population with different levels of physical activity, either in the model only adjusted for age (F = 2.127, P = 0.120) or in the model adjusted for demographics and lifestyle (F = 1.227, P = 0.294). The gender-stratified analysis also produced insignificant results. Our study confirmed a non-significant association between physical activity and telomere length in the northern Chinese population, which adds to the inconsistent association between physical activity and telomere length across different ethnic populations.
Adult ; Asian Continental Ancestry Group ; genetics ; China ; Cohort Studies ; Cross-Sectional Studies ; Exercise ; physiology ; Female ; Humans ; Male ; Middle Aged ; Telomere ; Young Adult

OBJECTIVETo evaluate the community-based health promotion effect of physical activity.

METHODSThe residents aged 18 and above from two communities in Gongshu District of Hangzhou City, Zhejiang province, were randomly selected and recruited for the multi-strategy and comprehensive physical activity intervention. Questionnaire survey, physical check up and blood biochemistry were conducted.

RESULTSAfter this two-year intervention, the time of the participant spent on weekly physical activity of moderate intensity increased from 464 min to 542 min (P<0.05), with an average increase of 78 min. Time spent in walking every week increased from 533 min to 678 min (P<0.05), with an average increase of 145 min. The body weight, waistline, blood pressure and heart rate all reduced significantly (P<0.05); the vital capacity increased significantly (P<0.05); and the related biochemical indicators were also improved.

CONCLUSIONComprehensive and evidence-based physical activity interventions targeting community population can improve the levels of physical activity, related body measurement and biochemical indicators.

Data Collection ; Female ; Health Promotion ; methods ; Humans ; Male ; Middle Aged ; Motor Activity ; Surveys and Questionnaires ; Time Factors

BACKGROUNDBladder urothelial cancer has been diagnosed at an increasing rate among young adults in China while the clinical outcomes remain highly controversial. To optimize the management of young patients with bladder cancer, we examined whether bladder urothelial cancer in young patients behaved differently from that in the elder patients.

METHODSFrom 1994 to 2008, a database of bladder urothelial cancer patients at a major tertiary medical center was retrospectively reviewed. The clinical and pathological parameters of patients who were less than 40 years of age and a series of patients older than 40 years of age as the control group during the same period were compared. A survival analysis was performed using the Kaplan-Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinic outcomes.

RESULTSYoung bladder cancer patients had a lower male-to-female ratio and were less likely to have advanced stages and high-grade cancers at the initial diagnosis. Tumors in young bladder cancer patients tended to be less multifocal at diagnosis. In addition, young patients had a lower recurrence rate and longer recurrence interval than older patients. The Kaplan-Meier curve and Log-rank test showed that young patients had significantly better cancer specific survival than old patients. The univariate and multivariate Cox regression analysis revealed that tumor grade is the sole predictor for tumor recurrence in young patients.

CONCLUSIONSYoung patients with bladder cancer have favorable pathological features and clinical outcomes than older patients. These findings argue for more conservative management approaches for young patients with bladder cancer.

Adolescent ; Adult ; Age Factors ; Child ; Female ; Humans ; Male ; Retrospective Studies ; Sex Factors ; Urinary Bladder Neoplasms ; pathology ; Urothelium ; pathology ; Young Adult

Objective To study the relevant factors on an measles outbreak caused by imported new virus (d11 genotype)from Myanmar and to develop effective strategies and measures.Methods On-site investigation on the outbreak was carried out. Results There were four townships (66%) in Menglian county reported 15 cases of measles, with 7 cases aged 6 months to 5 years old, 2 cases with the history of measles vaccination (MV). Another 8 cases were 21 to 49 year-olds but their histories on immunization were unclear. 14 of the measles cases with Myanmar citizenship came to China for treatment. They were aged 10 months to 13 years old, with only one case had ever received MV vaccination. For all the 29 cases, except for one case who did not adopt the sample case of Myanmar, the remaining 28 patients were positive for measles IgM antibodies. 6 cases of measles virus RNA were detected in the amplified sequence which showed genotype d11, and was considered Myanmar imported wild virus. 184 people received the MV inoculation, with a rate of 61.96% and the serum samples showed a measles IgG antibody positive rate of 87.50%. Manner MV emergency vaccination was carried out timely in that county so the measles outbreak was effectively controlled.Conclusion Imported measles cases from foreign countries might lead to epidemic, indicating the difficulty and challenge in the elimination of measles in our province. Emergent vaccination of MV could interrupt the transmission of the disease. Our experience showed that MV was effective in the prevention of d11 genotypes measles infection in the area.

OBJECTIVETo investigate the T lymphocyte subgroups and the levels of serum zinc (Zn), selenium (Se), iron (Fe), copper (Cu) in patients with diarrhea type of irritable bowel syndrome (D-IBS).

METHODSA total of 30 D-IBS patients and 30 control subjects were enrolled in this study, and their peripheral blood samples were collected. The percentage of peripheral CD3, CD4, CD8 T lymphocytes were analyzed by flow cytometry, and the ratio of CD4/CD8 was calculated. Serum Zn, Fe and Cu levels were determined by atomic absorption spectrometry(AAS), and the Se level by atomic fluorometry.

RESULTCompared with control group,the percentage of CD4 T lymphocyte and the ratio of CD4/CD8 in D-IBS group were significantly lower (P<0.01). However, there was no significant difference in serum Zn, Se, Fe, Cu levels between two groups (P>0.05).

CONCLUSIONThe declines of peripheral blood CD4 T lymphocytes and the ratio of CD4/CD8 may suggest a cellular immune abnormality in D-IBS patients. There was no significant difference in trace elements levels between the two groups.

Adult ; CD4-CD8 Ratio ; Case-Control Studies ; Copper ; blood ; Diarrhea ; etiology ; Female ; Humans ; Iron ; blood ; Irritable Bowel Syndrome ; blood ; complications ; immunology ; Male ; Middle Aged ; Selenium ; blood ; T-Lymphocyte Subsets ; immunology ; Trace Elements ; blood ; Zinc ; blood

OBJECTIVETo evaluate reimplantation of devitalized autogenous calvarial bone flaps and the fixation of titanium clamps (CranioFix) for cranioplasty.

METHODSFrom March 2000 to December 2003, 21 patients underwent (1) delayed reimplantation of preserved autogenous bone flaps, which were removed during the initial operations for increased intracranial pressure and stored in a freezer and autoclaved before use, or (2) immediate reimplantation of tumor invaded bone flaps that were devitalized by boiling. All of these flaps were fixed with titanium clamps (CranioFix). Resorption of the bone flaps was monitored by skull roentgenograms and computed tomography (CT). The clinical and aesthetic results were evaluated.

RESULTSDuring the follow-up period of 6 to 30 months, no complications were found. There was slight resorption of the bone flaps in all cases, but the edge of the bone flaps was within the range of the titanium clamps according to skull roentgenograms and CT. Clinical and aesthetic results were highly satisfactory.

CONCLUSIONSIt is simple and practical using devitalized autogenous calvarial bone flaps for cranioplasty. The firmness decreasing of the reimplanted bone flap due to resorption can be prevented greatly by titanium clamps (CranioFix).

Adolescent ; Adult ; Aged ; Bone Transplantation ; methods ; Craniotomy ; methods ; Female ; Humans ; Middle Aged ; Skull ; surgery ; Surgical Flaps ; Titanium ; Transplantation, Autologous ; Young Adult

OBJECTIVETo investigate the efficacy of interferon-alpha (IFN-alpha) therapy for HBeAg-negative chronic hepatitis B.

METHODSSixty-five Chinese HBeAg-negative chronic hepatitis B patients were treated with 5 MU recombinant rIFN-alpha 1b subcutaneously thrice weekly for 5 to 24 months, followed by 12 months of treatment-free follow-up; one hundred and eighty-eight Chinese HBeAg-positive patients served as controls. For each patient, serum alanine transaminase (ALT) was measured biochemically and serum HBV DNA level was detected with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay every 1 to 3 months during therapy and during the follow-up period. HBeAg loss (only for HBeAg-positive cases), HBV DNA undetectable, and ALT normalization: the three together were considered a combined response.

RESULTSRates of combined response were similar in HBeAg-negative patients (58.5%, 38/65) or HBeAg-positive ones at the end of treatment (weighted chi square test, chi2 = 1.878, P<0.05), but were higher at the end of the follow-up period in the HBeAg-negative cases (75.4%, 49/65) (weighted chi square test, chi2 = 4.796, P<0.05). Furthermore, relapse rates at the end of the follow-up period, were also similar in HBeAg-negative patients (15.8%, 6/38) or HBeAg positive (chi2 = 0.205, P>0.05). Combined response was achieved at a median of 6.0 months (2-16 months) of treatment course in HBeAg-negative patients while at a median of 6.0 months (1-22 months) in HBeAg-positive cases (Z = -0.186, P>0.05, by the Wilcoxon rank sum test). The only factor predictive of combined response, by binary logistic regression analysis, was inflammatory activity in the liver biopsy. Gender, age, baseline ALT level, baseline HBV DNA level, and anti-HBe were not predictive factors.

CONCLUSIONInterferon-alpha therapy induces a similar primary and sustained response in HBeAg-negative and in HBeAg-positive chronic hepatitis B patients.

Female ; Follow-Up Studies ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; immunology ; therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Treatment Outcome