Dental pulp stem cell-derived exosomes revitalize salivary gland epithelial cell function in NOD mice via the GPER-mediated cAMP/PKA/CREB signaling pathway.

BACKGROUND: Restoration of salivary gland function in Sjogren's syndrome (SS) is still a challenge. Dental pulp stem cells (DPSCs) derived exosomes had shown anti-inflammatory, anti-oxidative, immunomodulatory, and tissue function restorative abilities. However, the salivary gland function restoration potential of DPSCs-derived exosomes (DPSC-Exos) during SS has not been investigated yet. METHODS: DPSC-Exos was isolated by ultracentrifugation methods and characterized. Salivary gland epithelial cells (SGEC) were treated with interferon-gamma (IFN-γ) to mimic SS in vitro and cultured with or without DPSC-Exos. SGEC survival and aquaporin 5 (AQP5) expression were analyzed. mRNA sequencing and bioinformatics analysis were performed in IFN-γ vs. DPSC-Exos+ IFN-γ treated SGEC. Non-obese diabetic (NOD)/ltj female mice (SS model), were intravenously administered with DPSC-Exos, and salivary gland functions and SS pathogenicity were analyzed. Furthermore, the mRNA sequencing and bioinformatics predicted mechanism of the therapeutic effect of DPSC-Exos was further investigated both in vitro and in vivo using RT-qPCR, Western blot, immunohistochemistry, immunofluorescence, flowcytometry analysis. RESULTS: DPSC-Exos partially rescued IFN-γ triggered SGEC death. IFN-γ inhibited AQP5 expression in SGEC and DPSC-Exos reversed this effect. Transcriptome analysis showed GPER was the upregulated DEG in DPSC-Exos-treated SGEC with a positive correlation with salivary secretion-related DEGs. Pathway enrichment analysis revealed that DEGs were mainly attributed to estrogen 16 alpha-hydroxylase activity, extracellular exosome function, cAMP signaling, salivary secretion, and estrogen signaling. Intravenous injection of DPSC-Exos in NOD/ltj mice alleviated the SS syndrome as indicated by the increased salivary flow rate, attenuated glandular inflammation, and increased AQP5 expression. GPER was also upregulated in the salivary gland of DPSC-Exos-treated NOD/ltj mice compared with the PBS-treated NOD/ltj mice. IFN-γ+DPSC-Exos-treated SGEC showed higher expression of AQP5, p-PKA, cAMP, and intracellular Ca2+ levels compared with IFN-γ-treated SGEC. These effects were reversed by the inhibition of GPER. CONCLUSIONS: Our results showed that DPSC-Exos revitalize salivary gland epithelial cell function during SS via the GPER-mediated cAMP/PKA/CREB pathway suggesting the possible therapeutic potential of DPSC-Exos in SS-treatment.

A one-stop approach to diagnosing hereditary colorectal cancer in the Chinese population.

BACKGROUND AND AIM: The current procedure for identifying hereditary colorectal cancer (HCRC) is time consuming in clinical practice. This study aimed to develop a time-saving approach to diagnosing HCRC. METHODS: A total of 100 suspected HCRC patients were prospectively enrolled (cohort 1) and 116 colorectal cancer patients with DNA mismatch repair-deficient were retrospectively included (cohort 2). Next-generation sequencing (NGS) tests were performed on tumors and matched white blood cells (WBCs) or normal tissues. Using the conventional method upon WBC/normal tissue-based NGS data as a reference, the performance of the ColonCore method using tumor-only-based NGS data in predicting germline variants was explored in cohort 1 and validated in cohort 2. RESULTS: In cohort 1, the ColonCore method diagnosed 17 Lynch syndrome (LS) and 14 familial adenomatous polyposis (FAP); and by the conventional method, the cases were 16 and 10, respectively. The ColonCore method showed sensitivities of 100% in diagnosing LS (positive predictive value [PPV] 94.1%) and FAP (PPV 71.4%). Moreover, two of seven patients with multiple adenomas/polyps who did not meet existing clinical criteria for HCRC were predicted to harbor germline variants in APC and MUTYH. Additionally, the sensitivity of the ColonCore method in identifying LS patients from cohort 2 reached 85.7% with a PPV of 85.7%. CONCLUSION: The ColonCore method might be an acceptable tool for predicting germline variants associated with HCRC. Our work indicates the essentiality of NGS tests in CRC patients for precision diagnosis and treatment.

Spin-gapless van der Waals heterostructure for spin gating through magnetic injection devices.

Spin-gapless semiconductors (SGSs) are new magnetic zero-bandgap materials whose band structure is extremely sensitive to external influences (pressure or magnetic fields) and have great potential for high-speed and low-energy spintronics applications. The first-principles method was used to systematically study the heterostructures constructed of an asymmetric surface-functionalized Janus MXene material, Cr2NOF, and a two-dimensional hexagonal lattice (2DH) semiconductor material and to study the effects of the electronic structure, Curie temperature, magnetism, and the design of unusual band structures and magnetic injection in the bilayer to obtain an SGS structure. Through the design and construction of Cr2NOF/2DH van der Waals heterojunction spintronic devices, the spin-filtering effect of the devices can reach 100%, especially, realizing spin gating through magnetic injection. We report the transport mechanism of the heterojunction spintronic devices to achieve the goal of a controllable optimization of the device functions, which provides a theoretical basis for the design of MXene van der Waals heterojunctions for high-efficiency and low-power-consumption spintronic devices.

Interface engineering strategy for multisource spintronic devices via TMPS4 modulation of black-phosphorus.

Interface engineering is an effective strategy for significantly providing performance improvements in logic operations and information storage techniques, given the quantum effects characteristic of pristine two-dimensional ferromagnetic (FM) materials. Furthermore, the van der Waals (vdW) heterostructures enable a more efficient design of logic components. Herein, two novel designs of van der Waals heterostructures are proposed, black-phosphorus (BP)/TMPS4(TM = Cr, Fe-Mn), where the CrPS4 relies on odd and even layers for FM state - antiferromagnetic (AFM) state alternation, which is used to modulate BP with high hole mobility but no magnetism. Based on the first principles, the simulation results show that the two heterojunctions exhibit high stability, carrier mobility, and thermoelectric effects, of which the BP/CrPS4 heterojunction is specifically modulated to a type II electronic bandstructure. These two structures are applied in multi-source logic devices. The device performances show that the devices have spin Sebeck effect (SSE), perfect spin filtering effect (SFE), high extinction ratio (1347), and high thermal magnetoresistivity (1011). The above results suggest BP/TMPS4 bilayers as promising candidates for spin-based vdW devices and facilitate the future development of atomically thin magnetic information storage.

Letter to the Editor: An ultra-sensitive assay using cell-free DNA fragmentomics for multi-cancer early detection.

Early detection can benefit cancer patients with more effective treatments and better prognosis, but existing early screening tests are limited, especially for multi-cancer detection. This study investigated the most prevalent and lethal cancer types, including primary liver cancer (PLC), colorectal adenocarcinoma (CRC), and lung adenocarcinoma (LUAD). Leveraging the emerging cell-free DNA (cfDNA) fragmentomics, we developed a robust machine learning model for multi-cancer early detection. 1,214 participants, including 381 PLC, 298 CRC, 292 LUAD patients, and 243 healthy volunteers, were enrolled. The majority of patients (N = 971) were at early stages (stage 0, N = 34; stage I, N = 799). The participants were randomly divided into a training cohort and a test cohort in a 1:1 ratio while maintaining the ratio for the major histology subtypes. An ensemble stacked machine learning approach was developed using multiple plasma cfDNA fragmentomic features. The model was trained solely in the training cohort and then evaluated in the test cohort. Our model showed an Area Under the Curve (AUC) of 0.983 for differentiating cancer patients from healthy individuals. At 95.0% specificity, the sensitivity of detecting all cancer reached 95.5%, while 100%, 94.6%, and 90.4% for PLC, CRC, and LUAD, individually. The cancer origin model demonstrated an overall 93.1% accuracy for predicting cancer origin in the test cohort (97.4%, 94.3%, and 85.6% for PLC, CRC, and LUAD, respectively). Our model sensitivity is consistently high for early-stage and small-size tumors. Furthermore, its detection and origin classification power remained superior when reducing sequencing depth to 1× (cancer detection: ≥ 91.5% sensitivity at 95.0% specificity; cancer origin: ≥ 91.6% accuracy). In conclusion, we have incorporated plasma cfDNA fragmentomics into the ensemble stacked model and established an ultrasensitive assay for multi-cancer early detection, shedding light on developing cancer early screening in clinical practice.

The pattern and treatment outcomes for rectal cancer with concurrent locoregional recurrence and distant metastases after total mesorectal excision.

BACKGROUND: To study the pattern and treatment outcome of rectal cancer (RC) with concurrent locoregional recurrence (LR) and distant metastasis (DM) after total mesorectal excision (TME) and to identify patient-, disease-, and treatment-related factors associated with differences in prognosis after concurrent LR and DM. METHODS: RC patients who were diagnosed with concurrent LR and DM after TME from May 2015 to June 2019 were included in our study. All patients received single or multiple treatment modalities under the guidance of multidisciplinary team (MDT) of colorectal cancer in Fudan University Shanghai Cancer Center. The prognostic value of various clinicopathological factors for survival were calculated by Kaplan-Meier curves and Cox regression analyses. RESULTS: A total of 74 RC patients with concurrent LR and DM who had undergone TME with a median follow-up of 27 months were eligible for analysis. The median survival of the included patients was 34 months, and 30 patients (41%) died. Fifty-nine patients (80%) underwent comprehensive treatments. Patients with oligometastatic disease (OMD) achieved no evidence of disease (NED) status more frequently than those with multiple metastases (P = 0.003). In the univariate analysis, patients achieving NED, diagnosed with OMD and five or less peritoneal metastases tended to have longer survival after LR and DM diagnosis (P < 0.05). In the multivariate analysis, attaining NED status was the only independent factor for survival (hazard ratio (HR), 2.419; P = 0.032). Survival after concurrent LR and DM in the non-NED group was significantly shorter than that in the NED group (median survival, 32 vs. 46 months; HR, 2.7; P = 0.014). CONCLUSIONS: The pattern and treatment outcome of RC with concurrent LR and DM after TME has changed with the development of multiple treatment modalities. Although the prognosis remains poor, pursuing NED status through comprehensive treatments may improve the survival of RC patients with concurrent LR and DM after TME.

A first-principles study of the ultra-high spin rectification effect based on nitride MXenes (Sc2NO2, Ti2NO2).

Nitride MXenes exhibit inherent strong chemical stability and ferromagnetic properties, which are significant for their application in nanoscale spintronic devices. To demonstrate the potential of nitride MXenes in spintronics, we have designed a Sc2NO2/Ti2NO2 heterojunction and investigated its spin transport properties using first principles calculations combined with the non-equilibrium Green's function. The results show that the Sc2NO2/Ti2NO2 heterojunction has a stable negative differential resistance effect and a great spin rectification effect with a rectification ratio of 1.73 × 1011. The corresponding energy band structures and the transport behavior establish the mechanism for such properties. In addition, the perfect two-dimensional morphology provides a suitable nanostructured material for developing spintronic devices.

HIF1α promotes tumor chemoresistance via recruiting GDF15-producing TAMs in colorectal cancer.

Chemoresistance is a tremendous challenge to efficacy of systemic chemotherapy which is the preferred treatment for the advanced CRC patients. More tumor-associated macrophages (TAMs) are recruited into the CRC tumor under chemotherapy, which are highly implicated in the chemoresistance development, but the underlying molecular mechanism is unclear. Here, we present that activated HIF1α signaling in CRC cells under chemotherapy drives the expression of HMGB1to promotes macrophage infiltration and in turn chemoresistance development. Chemotherapeutic treatment with 5-FU leads to increased recruitment of macrophages into tumors, which display tumor-protective alternative activation. Mechanistically, tumor HIF1α signaling activated by chemo-induced ROS drives the transcription of HMGB1 to promote more macrophage infiltration into CRC tumor. Furthermore, high levels of GDF15 produced by TAMs impair the chemosensitity of tumor cells via enhancing fatty acids ß-oxidation. Together, our current study reveals a new insight into the cross-talking between tumor cells and immune cells, and provides novel drug targets for clinic treatments for CRC.

Comparison of long-term outcomes between Lynch sydrome and sporadic colorectal cancer: a propensity score matching analysis.

BACKGROUND: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. Comparison of prognosis between LS and sporadic CRC (SCRC) were rare, with conflicting results. This study aimed to compare the long-term outcomes between patients with LS and SCRC. METHODS: Between June 2008 and September 2018, a total of 47 patients were diagnosed with LS by genetic testing at Fudan University Shanghai Cancer Center. A 1:2 propensity score matching was performed to obtain homogeneous cohorts from SCRC group. Thereafter, 94 SCRC patients were enrolled as control group. All of enrolled patients received curative surgeries and standardized postoperative monitoring. The long-term survival rates between the two groups were compared, and the prognostic factors were also analyzed. RESULTS: The 5-year overall survival rate of LS group was 97.6%, which was significantly higher than of 82.6% for SCRC group (χ2 = 4.745, p = 0.029). The 5-year recurrence free survival rate showed no significant differences between the two groups (78.0% for LS group vs. 70.6% for SCRC patients; χ2 = 1.260, p = 0.262). The 5-year tumor free survival rates in LS group was 62.1% for LS patients, which were significantly lower than of 70.6% for SCRC group (χ2 = 4.258, p = 0.039). Subgroup analysis of recurrent patients show that the LS group had longer overall survival than the SCRC group after combined chemotherapy. By multivariate analysis, we found that tumor recurrence of primary CRC [Risk ratio (95% (confidence interval): 48.917(9.866-242.539); p < 0.001] and late TNM staging [Risk ratio (95% (confidence interval): 2.968(1.478-5.964); p = 0.002] were independent risk factors for OS. CONCLUSION: LS patients have better long-term survival prognosis than SCRC patients, even though the two groups have statistically comparable recurrence free survival. Combined chemotherapy is an effective treatment for LS patients who developed primary CRC recurrence. Standardized postoperative monitoring for LS patients may enable detection of metachronous tumors at earlier stages, which was a guarantee of a favorable prognosis despite lower tumor free survival.

Multiparametric MRI-based radiomics signature for preoperative estimation of tumor-stroma ratio in rectal cancer.

OBJECTIVE: To determine whether a radiomics signature (rad-score) outperforms ADC in TSR estimation by developing a radiomics biomarker for preoperative TSR diagnosis in rectal cancer. METHODS: This study included 149 patients (119 and 30 in the training and validation cohorts, respectively). All patients underwent T2-weighted, diffusion-weighted, and contrast-enhanced T1-weighted imaging. A rad-score was generated using the least absolute shrinkage and selection operator (LASSO) algorithm and stepwise multivariate logistic regression. Meanwhile, the mean ADCs were calculated from ADC maps. For both the mean ADC and rad-score, binary logistic regression and Spearman correlation coefficients were used to determine associations with the TSR, and the area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic performance. The reliability of the rad-score was quantified by comparing the imaging-estimated TSR with the actual TSR of each patient. RESULTS: Both the mean ADC and rad-score were positively correlated with the TSR in the training cohort (mean ADC: p < 0.001, r = 0.566; rad-score: p < 0.001, r = 0.559) and validation cohort (mean ADC: p < 0.001, r = 0.671; rad-score: p = 0.002, r = 0.536). The rad-score, with AUCs of 0.917 (95% CI 0.869-0.965) and 0.787 (95% CI 0.602-0.972) in the training and validation cohorts, respectively, outperformed the mean ADC (training cohort: AUC = 0.776, 95% CI 0.693-0.859; validation cohort: AUC = 0.764, 95% CI 0.592-0.936) in TSR estimation. CONCLUSION: The ADC possesses potential diagnostic value for TSR estimation in rectal cancer, and the rad-score shows increased diagnostic value over the ADC and may be a promising supplemental tool for patient stratification and informing decision-making. KEY POINTS: • Tumor-stroma ratio has been verified as an independent prognostic factor for various solid tumors including rectal cancer. • The ADC and multiparametric MRI-based radiomics features were significantly and positively correlated with the tumor-stroma ratio in rectal cancer. • The radiomics signature outperformed the ADC in discriminating TSR in rectal cancer.

The impact of COVID-19 pandemic on colorectal cancer patients: a single-center retrospective study.

BACKGROUND: Since December 2019, China has experienced a public health emergency from the coronavirus disease, which has become a pandemic and is impacting the care of cancer patients worldwide. This study evaluated the impact of the pandemic on colorectal cancer (CRC) patients at our center and aimed to share the lessons we learned with clinics currently experiencing this impact. METHODS: We retrospectively collected data on CRC patients admitted between January 1, 2020 and May 3, 2020; the control group comprised patients admitted between January 1, 2019 and May 3, 2019. RESULTS: During the pandemic, outpatient volumes decreased significantly, especially those of nonlocal and elderly patients, whereas the number of patients who received chemotherapy and surgery remained the same. During the pandemic, 710 CRC patients underwent curative resection. The proportion of patients who received laparoscopic surgeries was 49.4%, significantly higher than the 39.5% during the same period in 2019. The proportion of major complication during the pandemic was not significantly different from that of the control group. The mean hospital stay was significantly longer than that of the control group. CONCLUSIONS: CRC patients confirmed to be infection-free can receive routine treatment. Using online medical counseling and appropriate identification, treatment and follow-up can be effectively maintained. Adjuvant and palliative chemotherapy should not be discontinued. Endoscopic polypectomy, elective, palliative, and multidisciplinary surgeries can be postponed, while curative surgery should proceed as usual. For elderly CRC patients, endoscopic surgery and neoadjuvant radiotherapy are recommended.

Auditory filter-bank compression improves estimation of signal-to-noise ratio for speech in noise.

Signal-to-noise ratio (SNR) estimation is necessary for many speech processing applications often challenged by nonstationary noise. The authors have previously demonstrated that the variance of spectral entropy (VSE) is a reliable estimate of SNR in nonstationary noise. Based on pre-estimated VSE-SNR relationship functions, the SNR of unseen acoustic environments can be estimated from the measured VSE. This study predicts that introducing a compressive function based on cochlear processing will increase the stability of the pre-estimated VSE-SNR relationship functions. This study demonstrates that calculating the VSE based on a nonlinear filter-bank, simulating cochlear compression, reduces the VSE-based SNR estimation errors. VSE-SNR relationship functions were estimated using speech tokens presented in babble noise comprised of different numbers of speakers. Results showed that the coefficient of determination (R2) of the estimated VSE-SNR relationship functions have absolute percentage improvements of over 26% when using a filter-bank with a compressive function, compared to when using a linear filter-bank without compression. In 2-talker babble noise, the estimation accuracy is more than 3 dB better than other published methods.

Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: A single-center retrospective study of 1,834 Chinese patients with Stage I-IV colorectal cancer.

Mutations of KRAS, NRAS, BRAF and DNA mismatch repair (MMR) status have become an important part of the assessment of patients with colorectal cancer (CRC), while respective clinicopathologic features and prognostic significance in specific stages and related detection strategies remain unclear. We retrospectively analyzed clinicopathologic features and prognosis of 1,834 patients with Stage I-IV colorectal adenocarcinoma. Mutations in KRAS, NRAS and BRAF and DNA MMR status were determined. The mutation rates of KRAS, NRAS and BRAF were 46.4, 3.2 and 3.5%, respectively, and the mismatch repair gene deletion (dMMR) rate was 5.6%. In a multivariate analysis, female, advanced age, tumor type histology, mucinous carcinoma and positive tumor deposits were associated with a high KRAS mutation rate. A high BRAF mutation rate was associated with female, poor differentiation, lymphovascular invasion and positive tumor deposits. Factors associated with high dMMR rates included low age, large tumor size, poor differentiation, Stages I-III. Tumor site was independently associated with KRAS mutation, BRAF mutation and dMMR. KRAS and BRAF mutations were independent risk factors for shorter overall survival (OS) in Stage IV tumors but not in Stage I-III tumors. NRAS mutation was an independent risk factor for shorter OS in Stage I-II tumors. dMMR was independently associated with longer OS in Stage III tumors.

Laparoscopic surgery may decrease the risk of clinical anastomotic leakage and a nomogram to predict anastomotic leakage after anterior resection for rectal cancer.

INTRODUCTION: Anastomotic leakage is still one of the most dreaded complications after anterior resection for rectal cancer. This study aimed to identify risk factors for anastomotic leakage and to create a nomogram for precise prediction of anastomotic leakage after anterior resection for rectal cancer. METHODS: Two thousand six hundred eighteen consecutive patients who underwent anterior resection for rectal cancer with primary anastomosis, with or without diverting stoma, were retrospectively analyzed as a training dataset. Univariate and multivariable Cox regression analyses were used to determine independent risk factors associated with anastomotic leakage. A nomogram was constructed to predict anastomotic leakage. Data containing 611 patients were prospectively collected as a test dataset. The performance of the nomogram was evaluated by using a bootstrapped-concordance index and calibration plots. RESULTS: The rate of clinical anastomotic leakage was 9.3% in the training dataset. Multivariate analysis identifies the following variables as independent risk factors for anastomotic leakage: gender (male) (odds ratio (OR) = 2.286), distance of tumor to anal verge (OR = 0.791), tumor size (OR = 1.175), operating time (OR = 1.009), diabetes mellitus (OR = 1.704), laparoscopic surgery (OR = 0.445), anastomotic bleeding (OR = 13.46), and diverting stoma (OR = 0.386). We created a nomogram with high discriminative ability (concordance index, 0.722). The area under the curve value, which evaluated the predictive performance of external validation, was 0.723. CONCLUSIONS: A protective diverting stoma and laparoscopic surgery significantly decrease the risk of anastomotic leakage. Our nomogram was a useful tool for precise prediction of anastomotic leakage after anterior resection for rectal cancer.

A negative-doughnut distal resection margin less than 5 mm does not affect prognosis in rectal cancer.

AIM: Many issues relating to the distal margin of anterior resection of the rectum still exist. We aimed to investigate whether negative distal resection margin (DRM) and positive DRM in the main specimen with negative doughnut has equivalent prognosis in patients with rectal cancer. METHODS: We included 287 patients with rectal cancer, including 69 cases with positive margins and 218 cases with negative margins, all of whom underwent regular follow-up. Survival rate was calculated using Kaplan-Meier survival analysis, while the log-rank test was used to determine statistical difference. Prognostic factors were found using the Cox regression model. RESULTS: There was no significant difference in clinicopathological features between the two groups with the exception of tumor location. Positive findings in the DRM with negative findings in the doughnut resection do not affect the overall survival, local recurrence, or distant metastasis. Factors relating to resection margin, such as the length of resection, negative, or positive findings, were not found to be prognostic. CONCLUSION: Given postoperative pathology results with positive DRM but negative findings in the doughnut resection, a second surgery was not necessary. Instead, adjuvant radiochemotherapy and close follow-up will suffice.

Effect of auditory efferent time-constant duration on speech recognition in noise.

The human auditory efferent system may play a role in improving speech-in-noise recognition with an associated range of time constants. Computational auditory models with efferent-inspired feedback demonstrate improved speech-in-noise recognition with long efferent time constants (2000 ms). This study used a similar model plus an Automatic Speech Recognition (ASR) system to investigate the role of shorter time constants. ASR speech recognition in noise improved with efferent feedback (compared to no-efferent feedback) for both short and long efferent time constants. For some signal-to-noise ratios, speech recognition in noise improved as efferent time constants were increased from 118 to 2000 ms.

Comparative study of single-center patients with thyroid metastases from colorectal cancer and previously reported cases in the literature.

BACKGROUND: Thyroid metastases from colorectal cancer (CRC) are rare, both in clinical practice and in the literature; hence, their diagnosis, appropriate treatment, and prognostic factors require further investigations. METHODS: A retrospective analysis was performed for four cases of thyroid metastases from CRC, treated in our center between January 2005 and December 2015, and the relevant literature was searched using PubMed, resulting in the identification of 17 patients with detailed information available. The clinical data and follow-up information of our patients and the previously reported cases were collected and compared. RESULTS: The median age of the 21 patients was 59 years (44.5 and 66 years for our patients and the previously reported cases, respectively). Fifteen (71.4%) primary tumors were distributed throughout the distal colon or rectum (75% [3/4] in our center and 70.5% [12/17] in the previously reported cases). According to our analysis, we found that 81.0% of patients (17/21) showed concomitant lung metastasis. Among them, all four patients in our center showed lung metastasis, and 75% (3/4) developed thyroid metastases after the lung metastasis. In the previously reported cases, the corresponding proportions were 76.5 and 76.5% (13/17) of patients, respectively. The median time after primary tumor diagnosis to thyroid metastasis development was 28 months (26 months in our center and 35 months in the previously reported cases). One patient with advanced CRC in our center died 5 months after the thyroid metastasis was identified, while the remaining three patients are currently alive (longest follow-up time, 27 months). The median survival time after thyroid metastasis during 3 years of follow-up of the previously reported 17 patients was 12 months. There was no difference in the overall survival between patients treated non-surgically (8/21) and patients undergoing thyroidectomy alone or thyroidectomy with adjuvant therapy (13/21) (p = 0.388). In addition, we found that the overall survival of the patients whose other metastases were treated with radical treatment was superior to that in those treated with palliative treatment (p = 0.022). CONCLUSIONS: Thyroid metastases from CRC are rare in clinical practice and are a manifestation of advanced CRC. The prognosis of patients with thyroid metastases from CRC is related to various factors, including the grade of malignancy of the primary lesion, the presence of other metastases, and whether the metastases are timely diagnosed and a radical treatment strategy is employed.

[Advance in research on the correlation between genotypes of susceptible mutations and clinical phenotype of familial adenomatous polyposis].

Familial adenomatous polyposis (FAP) is one of the most common hereditary colorectal cancers. Its intestinal and extra-intestinal manifestations are correlated with mutation sties of the APC gene. Potential gene modulation sites in patients who have typical clinical manifestations but with unidentified APC mutations are also discussed, which included MUTYH gene, AXIN gene and certain epigenetic changes. With the generalization of Precision Medicine, to offer individualized treatment and surveillance strategy based on the genotype-phenotype correlation will be of great value for FAP patients. This review focuses on the research advance in genotype - phenotype correlation studies of FAP patients.

Prognostic risk factors in patients with bone metastasis from colorectal cancer.

The morbidity of bone metastasis (BM) from colorectal cancer (CRC) is increasing more than ever; however, insufficient research on BM from CRC leads to reduced awareness of the issue. Therefore, the aim of this study was to evaluate the clinical features and prognostic risk factors of CRC patients with BM. Clinical data were retrospectively analyzed for a total of 242 CRC patients with BM. Of the 242 CRC patients with BM, 52 (21.5 %) had bone metastasis alone (BMA) and 190 (78.5 %) had both bone and visceral metastasis (BM&VM). The median survival time (MST) after the diagnosis of BM in all 242 patients was 15.6 months (95 % confidence interval [CI] 12.74-18.46 months). The MST of the BMA group was significantly longer than that of the BM&VM group (29.1 vs. 12.8 months, p = 0.003). Using a Cox proportional hazard model, we identified a high carcinoembryonic antigen (CEA) level and BMA as independent prognostic factors for CRC patients with BM. For the BMA group, the independent prognostic factors were elevated alkaline phosphatase (ALP) and perineural invasion of the primary cancer, which were distinct from the factors for the entire group of BM patients. Furthermore, we found that the BMA patients with multiple sites of BM had similar prognosis to the BM&VM patients. These findings together provide us with a further understanding of BM from CRC and reveal that BMA may be a distinct subset of BM from CRC that has unique independent prognostic factors and a good prognosis.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict chemotherapy outcomes and prognosis in patients with colorectal cancer and synchronous liver metastasis.

BACKGROUND: Recent evidence indicates that inflammatory parameters could be useful to predict metastasis from colorectal cancer. However, their roles in predicting chemotherapy response and prognosis in patients with synchronous colorectal liver metastasis (CLM) are unknown. METHODS: The clinical data and baseline laboratory parameters of 55 patients with synchronous CLM were retrospectively reviewed. All patients underwent palliative resection of the primary tumor and oxaliplatin-based chemotherapy. Two indices of systemic inflammation were reviewed-neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)-preoperatively and before the second cycle of chemotherapy. Associations between prognostic variables and tumor response, progression, and survival were investigated. RESULTS: NLR < 4 and PLR < 150 were correlated with better disease control (p = 0.024 and 0.026, respectively). In univariate analysis, elevated NLR and PLR were significant prognostic factors for poor overall survival (OS) and progression-free survival (PFS). In multivariate analysis, PLR (p = 0.027), age (p = 0.018), resection of liver metastases (p = 0.017), and lactate dehydrogenase level (p = 0.011) were independent predictors of PFS, while resection of liver metastases was the only independent predictor of OS (p = 0.002). In addition, when patients were divided into groups according to changes in NLR and/or PLR, reduced NLR and PLR were associated with improved disease control (p = 0.038 and 0.025, respectively). Normalization of NLR also was associated with improved PFS. CONCLUSIONS: NLR and PLR are potentially useful clinical biomarkers to predict chemotherapy response in patients with synchronous CLM. PLR also may be useful to predict PFS in these patients.