Colorectal Cancer Screening Program in Songjiang district,Shanghai between 2015 and 2017: Evaluation of participation rate and the associated factor

Little is known about the participation rate of newly implemented colorectal cancer (CRC) screening programs in China. Our goals were to identify factors associated with nonparticipation for CRC screening in Songjiang District, Shanghai.We analyzed individuals included in an observational cohort study from 4 towns (Xin Qiao, She Shan, Mao Gang, and Zhong Shan) in Songjiang District. The participation rate was calculated for the CRC screening program based on a fecal immunochemical test and a risk assessment questionnaire between 2015 and 2017 inclusive.Of the 27,130 individuals eligible for inclusion in this study, 20,863 (76.9%) participated in CRC screening at least once during 2015 and 2017. The factors linked with nonparticipation were; being male (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.82–0.93, P < .01), unmarried (OR 0.71, 95% CI 0.64–0.80, P < .01), having a high education level (middle school, OR 0.82, 95% CI 0.74–0.90, P < .01, high school or above, OR 0.64, 95% CI 0.57–0.73, P < .01), absence of chronic disease (OR 0.90, 95% CI 0.85–0.96, P < .01), and living in 2 out of the 4 towns covered (Xin Qiao, OR 0.72, 95% CI 0.66–0.78, P < .01, Zhong Shan, OR 0.29, 95% CI 0.26–0.31, P < .01).The current study revealed several associated factors with nonparticipation for the CRC screening in Songjiang district. These findings will help identify target populations that require an individualized approach to increase the participation rate.     

A dose-finding study of glycosylated G-CSF (Lenograstim) combined with CHOP therapy for stem cell mobilization in patients with non-Hodgkin's lymphoma

BACKGROUND: Peripheral blood stem cell (PBSC) reinfusion has been widely used for hematopoietic reconstitution after high-dose chemotherapy. However, the optimal dose of granulocyte colony-stimulating factor (G-CSF) for PBSC mobilization in combination with chemotherapy for autograft remains unknown. METHODS: To find the optimal dose of glycosylated G-CSF (lenograstim) for PBSC mobilization in combination with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), we conducted a dose-finding study on 43 newly diagnosed patients who had unfavorable prognostic factors. They received four to six courses of cyclophosphamide, doxorubicin, vincristine and prednisolone combined with lenograstim every 2 weeks (biweekly CHOP therapy). PBSC apheresis was started after the third course of biweekly CHOP therapy. Lenograstim was given daily from day 3 until the day of the last apheresis. The optimum dose of lenograstim was assessed based on mobilization efficacy and safety profiles at a daily single dose of 2, 5 and 10 microg/kg for eight patients in each level. RESULTS: The collected number of CD34+ cells in the first apheresis products was higher in the 5 microg/kg group than in the 2 microg/kg group (median, 4.22 x 10(6) vs 2.49 x 10(6) CD34+ cells/kg, P = 0.051). The highest dose of 10 microg/kg (median, 2.99 x 10(6) CD34+ cells/kg) failed to show a dose dependence in PBSC mobilization. The efficacy and safety of the 5 microg/kg dose were further confirmed in an additional 19 patients. CONCLUSIONS: The present study suggests that the recommended dose of lenograstim for PBSC mobilization with CHOP therapy in untreated NHL is 5 microg/kg.     

Two single nucleotide polymorphisms in <Emphasis Type="Italic">PRDM9</Emphasis> (<Emphasis Type="Italic">MEISETZ</Emphasis>) gene may be a genetic risk factor for Japanese patients with azoospermia by meiotic arrest

Purpose

To investigate whether defects in human PRDM9, CDK2 and PSMC3IP are associated with azoospermia Mutational analysis was performed in Japanese patients with azoospermia caused by meiotic arrest.

Methods

Mutational screening of the coding regions of human PRDM9, CDK2 and PSMC3IP was done by direct sequencing using genomic DNA from 18 Japanese patients. Statistical analysis of the detected coding single nucleotide polymorphisms (cSNPs) in patients and normal control men was then carried out.

Results

One cSNP was detected in CDK2 and PSMC3IP. There were no significant differences in genotype distribution and allele frequencies between the patient and control groups in these two genes. However, three novel cSNPs were detected in the PRDM9. The genotype and allele frequencies of heterozygotes in SNP2 and SNP3 of PRDM9 were significantly higher in the patient group than in the control group.

Conclusion

We found a possible association between PRDM9 and azoospermia by meiotic arrest.

     

The Simultaneous Onset of Pancreatitis and Colitis as Immune-related Adverse Events in a Patient Receiving Nivolumab Treatment for Renal Cell Carcinoma

Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy.     

Total syntheses of ent-hypocoprin A and ent-hypocoprin B

This study reports the stereoselective total syntheses of the antipodes of the unique 3/10 bicyclic skeletal sesquiterpenoids, namely, hypocoprin A and hypocoprin B. The synthesis involved conjugate addition accelerated by trimethylsilyl chloride, construction of the ten-membered ring via the intramolecular S_N2 reaction promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene, and osmium-mediated π-facial selective dihydroxylation to functionalize the 1,1-disubstituted alkene.

This study reports the stereoselective total syntheses of the antipodes of the unique 3/10 bicyclic skeletal sesquiterpenoids, namely, hypocoprin A and hypocoprin B.     

Does Systemic Chemotherapy Influence Skeletal Growth of Young Osteosarcoma Patients as a Treatment-Related Late Adverse Effect?

The aim of this study was to investigate the influence of systemic chemotherapy on the skeletal growth of young osteosarcoma patients as a treatment-related late adverse effect. We reviewed the height data of 20 osteosarcoma patients (13 males and 7 females) aged ≤18 years. The average (±SD) age at diagnosis was 14.5 (±3.3) years. The average follow-up interval was 89.6 months. After wide resection of the affected bones, reconstruction with tumor prostheses and auto-bone grafting was carried out in 11 and 9 cases, respectively. Pearson’s correlation coefficient was calculated to evaluate the association between actual and predicted (using Paley’s multiplier method) heights. Z-scores were used to compare the initial and final heights with the Japanese national growth curve. Actual and predicted heights were correlated according to Pearson’s correlation coefficient (R = 0.503). Z-analysis showed that statistical significance (p = 0.04) was noted for the height data Z-scores of patients between ≤10 years and >10 years at the final follow-up. Systemic chemotherapy did not reduce skeletal growth in young osteosarcoma patients as a late adverse effect based on two different evaluation methods. However, patients aged ≤10 years at diagnosis may develop a short stature after systemic chemotherapy.     

Urinary Transthyretin as a Biomarker in ATTRv Val50Met Amyloidosis

Transthyretin (TTR), the precursor protein for amyloidogenic TTR (ATTR) amyloidosis, forms tetramers and escapes glomerular filtration by binding with thyroxine and retinol-binding protein. However, variant TTRs are unstable as tetramers, so monomeric TTR has become the precursor protein of amyloid deposits, via protein misfolding. The aim of the study was to evaluate the utility of urinary TTR in the diagnosis of ATTRv amyloidosis. Urinary samples from healthy volunteers, ATTRv V50M amyloidosis patients, and asymptomatic carriers of the ATTRv V50M gene were analysed using ELISA. To analyse the different forms of TTR secreted to the urine, we performed Western blotting and mass spectrometry. Urinary TTR concentrations were significantly higher in the ATTRv V50M amyloidosis patients than they were in the healthy volunteers and asymptomatic carriers of the gene. Although the TTR concentrations were negligible in the healthy volunteers, they were correlated with disease progression and urinary albumin concentrations in the ATTRv V50M amyloidosis patients. The Western blotting and mass spectrometry revealed the presence of monomeric wild-type and variant TTRs in the urine. Urinary TTR concentrations may become a more sensitive biomarker of ATTRv progression than albumin.     

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Synaptic transmission and long-term potentiation (LTP) in the CA1 region of hippocampal slices have been studied during ageing of a double transgenic mouse strain relevant to early-onset familial Alzheimer's disease (AD). This strain, which over-expresses both the 695 amino acid isoform of human amyloid precursor protein (APP) with K670N and M671L mutations and presenilin 1 with the A246E mutation, has accelerated amyloidosis and plaque formation. There was a decrease in synaptic transmission in both wildtype and transgenic mice between 2 and 9 months of age. However, preparing slices from 14 month old animals in kynurenic acid (1 mM) counteracted this age-related deficit. Basal transmission and paired-pulse facilitation was similar between the two groups at all ages (2, 6, 9 and 14 months) tested. Similarly, at all ages LTP, induced either by theta burst stimulation or by multiple tetani, was normal. These data show that a prolonged, substantially elevated level of Aβ are not sufficient to cause deficits in the induction or expression of LTP in the CA1 hippocampal region.     

Distinct Recurrence Pattern and Outcome of Adenocarcinoma of the Gastric Cardia in Comparison with Carcinoma of Other Regions of the Stomach

Background Carcinoma arising in the cardioesophageal junction is a distinct clinical entity compared with tumors located in other regions of the stomach. The prognosis for adenocarcinoma of the upper stomach is considered to be relatively poorer than carcinomas of the more distal stomach. We have therefore investigated patients with carcinoma of the gastric cardia in order to evaluate the underlying cause of this poor prognosis. Materials and Methods Clinicopathologic features and postoperative prognosis of 101 patients with carcinoma of the cardia were evaluated and compared with findings on 1884 patients with tumors in other regions of the stomach. Results Tumors of the cardia had a mean size of 6.8 cm, which was significantly larger than the mean size of 5.9 cm for tumors found in the middle- and lower third of the stomach. The incidence of serosal invasion, lymph node metastasis, and lymphatic and blood vessel invasion was higher in association with adenocarcinoma of the cardia than with adenocarcinoma in remaining parts of the stomach. In the analysis of patients who had undergone curative resection, the 5-year survival rates were 61.6, 79.1, and 82.6% in patients with carcinoma of the cardia, upper one-third, and remaining middle- and lower one-third of the stomach, respectively, and the differences were statistically significant. Multivariate analysis indicated that adenocarcinoma of the gastric cardia is an independent prognostic factor. With regard to the site of recurrence, both lymph node and hematogenous recurrence were observed more frequently in the cardia than in the remaining parts of the stomach. Conclusions Our data indicate that the prognosis of patients with adenocarcinoma of the gastric cardia is extremely poor. To improve their prognosis, new treatments in addition to gastrectomy with extensive lymph node dissection are needed.