Lobaplatin hyperthermic intraperitoneal chemotherapy plus cytoreduction and rechallenge using cetuximab for wild-type RAS peritoneal metastatic colon cancer: a case report and literature review.

BACKGROUND: Synchronous peritoneal metastasis of colorectal cancer usually predicts a bleak prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) have brought a glimmer of hope to the treatment of peritoneal cancer. Few cases treated with lobaplatin have been reported in the literature and the regimen is controversial. In this case, the comprehensive treatment scheme of lobaplatin-based HIPEC plus CRS and rechallenge using cetuximab plus systemic chemotherapy is effective, especially for the patients with left colon cancer (wild-type RAS). CASE PRESENTATION: A 49 year-old man with signet ring cell carcinoma of sigmoid colon with extensive abdominal metastasis (wild-type RAS) was hospitalized with prolonged abdominal pain, distention and abdominal mass. After receiving HIPEC with lobaplatin and XELOX regimen combined with cetuximab for eight cycles, the patient had been treated with the FOLFIRI regimen and cetuximab for 24 cycles, which discontinued due to myelosuppression. Because the disease recurred unfortunately 4 months later, the FOLFIRI + cetuximab regimen was initiated again and stopped after two cycles. Intestinal obstruction occurred 1 month later, so open total colectomy, CRS + HIPEC and ileorectal anastomosis were performed. Capecitabine adjuvant chemotherapy was administered, followed by the maintenance therapy with FOLFIRI + cetuximab regimen. After that, the patient has been in relatively stable condition. By August 2021, the overall survival is more than 45 months, which displays significant curative effect. CONCLUSION: For peritoneal metastasis from left colon cancer, the management with CRS + lobaplatin HIPEC and rechallenge of systemic chemotherapy plus targeted medicine based on gene detection can dramatically improve prognosis and extend the overall survival.

Adjuvant chemotherapy benefits on patients with elevated carcinoembryonic antigen in stage IIA colon cancer: a SEER-based analysis.

OBJECTIVE: Indications for adjuvant chemotherapy in stage IIA (T3N0M0) colon cancer are still controversial. The purpose of this study was to evaluate the prognostic value of elevated carcinoembryonic antigen (CEA) levels for cancer-specific survival (CSS) and overall survival (OS) in patients with stage IIA colon cancer. We aimed to examine the impact of adjuvant chemotherapy on OS in stage IIA colon cancer patients with elevated CEA levels. METHODS: Patients with stage IIA colon cancer (N = 3477) diagnosed between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier and Cox proportional hazards regression models were used to assess the prognostic effect of CEA on CSS and OS. RESULTS: Cox regression analysis demonstrated that CEA was an independent risk factor for CSS and OS in patients with stage IIA colon cancer (CSS: HR = 2.001, 95% CI 1.603-2.499, P < 0.001; OS: HR = 1.530, 95% CI 1.335-1.752, P < 0.001). In the subgroup with elevated CEA, patients received adjuvant chemotherapy had a better OS compared with those did not (χ2 = 10.585, p = 0.001). CONCLUSION: CEA was an independent risk factor for CSS and OS in patients with stage IIA colon cancer. Patients with stage IIA colon cancer with an elevated CEA level might benefit from adjuvant chemotherapy.

Comparison of the outcomes of cytoreductive surgery versus surgery plus hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: a propensity score matching analysis.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective treatment options for selected patients with peritoneal carcinomatosis (PC). We compared the short-term outcomes of surgery plus HIPEC and CRS alone for PC. METHODS: We retrospectively examined patients who underwent CRS-HIPEC for PC at a single center from 2014 to 2019 using the Chinese CRS-HIPEC patient database at our institution. Patients were divided into two groups: surgery plus HIPEC (450) and surgery alone (200). A 1:1 propensity score matching (PSM) analysis was performed. The postoperative outcomes, mortality, and length of hospital stay were compared between the surgery plus HIPEC and CRS alone groups. RESULTS: Propensity scoring generated 162 pairs. There was no statistically significant difference in the 30-day mortality rate between the groups (0% vs 0%, P = 1.000), and the morbidity rates were similar in both groups (7.4% vs 8.0%, P = 0.835). The surgery plus HIPEC group had a longer operative time (247.81 ± 64.70 vs 184.55 ± 29.56, P ≤ 0.001) and a slightly longer postoperative hospital stay (14.64 ± 5.24 vs 12.59 ± 3.76, P ≤ 0.001). No other baseline characteristics were significantly different. CONCLUSIONS: Surgery plus HIPEC is feasible for select patients and is associated with prolonged surgery times and prolonged hospital stays, and there is no significant difference in mortality rates or postoperative outcomes.

A Retrospective Propensity Score Matched Study of the Preoperative C-Reactive Protein to Albumin Ratio and Prognosis in Patients with Resectable Non-Metastatic Breast Cancer.

BACKGROUND A retrospective study aimed to investigate the association between the CRP to albumin ratio and prognosis in patients with resectable non-metastatic breast cancer in terms of disease-free survival (DFS) and overall survival (OS) using propensity score matching. MATERIAL AND METHODS Patients with newly diagnosed resectable non-metastatic breast cancer (n=200) who underwent modified radical mastectomy between January 2008 to June 2013 included a group with an increased CRP to albumin ratio ≥0.029 (n=80) and a group with reduced CRP to albumin ratio <0.029 (n=120). Propensity score matching was used to estimate the prognostic role of the CRP to albumin ratio, and a 1: 1 matching using four covariates was performed to overcome selection bias. The prognostic significance of the CRP to albumin ratio was analyzed using receiver operating characteristic (ROC) curves. Kaplan-Meier survival analysis and a Cox proportional hazards model were conducted to identify the impact on DFS and OS. RESULTS An increased CRP to albumin ratio was associated with increased age, post-menopausal status, and a high risk of recurrence or death in patients with breast cancer. An increased preoperative CRP to albumin ratio was significantly associated with reduced disease-free survival (DFS) and overall survival (OS) (all P<0.05). Multivariate analysis showed that an increased CRP to albumin ratio was an independent risk factor for long-term outcome and predicted reduced DFS (HR, 2.225; P=0.024) and OS (HR, 9.189; P=0.003). CONCLUSIONS Preoperative evaluation of the CRP to albumin ratio was an independent prognostic indicator in patients with resectable breast cancer.

Propensity score analysis of recurrence for neutrophil-to-lymphocyte ratio in colorectal cancer.

BACKGROUND: The perioperative serum neutrophil-to-lymphocyte ratio (NLR) has been proposed to predict adverse prognosis in colorectal cancer (CRC). However, its interpretation remains unclear. The present study aimed to clarify the prognostic value of NLR in predicting survival among CRC patients. MATERIALS AND METHODS: A single-centre, retrospective, propensity score-matched study of adenocarcinoma patients who underwent D3 lymphadenectomy via laparoscopic or open surgery between 2010 and 2016 was conducted. A cutoff of 3.5 was used based on the receiver operating characteristic curve. To overcome selection biases, we performed a 1:1 match using six covariates. RESULTS: The high-preoperative NLR group had a higher recurrence rate than the low group (P < 0.001). Univariate analysis showed that increased NLR (P < 0.001), N1 (P = 0.016), and N2 (P < 0.001) were associated with worse recurrence-free survival (RFS). Multivariate analysis showed that N2 (hazard ratio [HR], 2.492; P = 0.008) was an adverse prognostic factor for RFS. Univariate analysis for overall survival (OS) revealed that high perioperative NLR (P = 0.001), N1 (P = 0.01), N2 (P < 0.001), and distant metastasis (P < 0.001) were adverse prognostic factors. Subsequent multivariate analysis showed that M1 (HR, 3.973; P < 0.001) and N2 (HR, 2.381; P = 0.013) were highly adverse factors for OS. Clinical assessments performed during a 21.14 (±16.20)-mo follow-up revealed that OS (P = 0.001) and RFS (P < 0.001) were worse in the high-perioperative group than in the low group between the matched groups. CONCLUSIONS: An elevated preoperative NLR is a strong predictor of worse RFS and OS in CRC patients.

Variation in the dielectric properties of freshly excised colorectal cancerous tissues at different tumor stages.

The study was designed to identify differences in the dielectric properties of ex vivo colorectal cancerous tissues at different tumor stages. To date, 130 freshly excised colorectal cancerous specimens underwent measurement of both relative permittivity and conductivity on the serosal and mucosal surfaces of the carcinoma nidus, and the mucosa of the surgical resection margin ranging from 50 to 500 MHz at the Larmor frequencies. Tumor node metastasis staging was determined according to pathological reports for each patient. There were statistically significant differences in the relative permittivity of both colorectal cancerous serosa and mucosa among stages ≤I, II, III, and IV and between stages ≤II and ≥III (P < 0.05) at most frequencies under 300 MHz; statistically significant differences in conductivity were also observed for most of the measured frequencies (P < 0.05). The significant differences in dielectric characteristics among tumor stages, especially between early and advanced stages, have value for selecting appropriate surgical strategies. The presented ex vivo data provide important information for magnetic resonance electrical properties tomography in vivo system because the frequencies of 64 MHz (1.5T) and 128 MHz (3T) are usually used in clinical settings. Bioelectromagnetics. 38:522-532, 2017. © 2017 Wiley Periodicals, Inc.

Polyamidoamine dendrimer liposome-mediated survivin antisense oligonucleotide inhibits hepatic cancer cell proliferation by inducing apoptosis.

Polyamidoamine dendrimer (PAMAM) is a new nanometer material, which can transfer the target genes to cells with high efficiency and lower toxicity. This study aims to evaluate antitumor effects of survivin antisense oligonucleotide (survivin-asODN) (carried by polyamidoamine dendrimer liposome) on hepatic cancer in nude mice. Hepatic cancer model was established by injecting SMMC-7721 cells subcutaneously into flanks of nude mice. Polyamidoamine dendrimer and liposome were mixed with survivin-asODN, respectively. The shape and size of complex were observed by transmission electron microscope, and zeta potential was measured by an analytical tool. Encapsulation efficiency and DNA loading level were determined by an ultraviolet spectrophotometer in centrifuging method. Expression of survivin in transplant tumor was measured by Western blotting. No significant difference appeared for diameter and envelopment ratio between PAMAM liposome-survivin-asODN and PAMAM-survivin-asODN (P > 0.05). Both zeta potential and transfection efficiency in PAMAM liposome-survivin-asODN were higher than that in PAMAM-survivin-asODN complex (P < 0.05). Expression of survivin protein and weight of tumors in transplanted tumors in PAMAM liposome-survivin-asODN group was less than that in PAMAM-survivin-asODN group (P < 0.05). Cell apoptosis rate in PAMAM liposome-survivin-asODN group was higher than that of PAMAM-survivin-asODN group (P < 0.05). In conclusion, polyamidoamine dendrimer liposome can deliver survivin-asODN into hepatic transplanted tumor cells effectively. Ployamidoamine dendrimer liposome-mediated survivin-asODN can inhibit hepatic cell proliferation by inducing apoptosis.

Reduced expression of E-cadherin correlates with poor prognosis and unfavorable clinicopathological features in gastric carcinoma: a meta-analysis.

BACKGROUNDS: Gastric carcinoma (GC) is one of the most fatal human malignancies globally, with a median survival time less than 1 year. E-cadherin exerts a crucial role in the development and progression of GC as an adhesive, invasive suppressor gene. Whether reduced E-cadherin has an impact on prognosis, clinicopathological features for GC has been well studied, but no conclusive results has been obtained. METHODS: Eligible studies and relevant data were obtained from PubMed, Elsevier, Embase, Cochrane Library and Web of Science databases until June 30, 2023. A fixed- or random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Correlation of E-cadherin expression with overall survival (OS), clinicopathological features and risk factors were evaluated. RESULTS: 36 studies fulfilled the selected criteria. 9048 cases were included. This meta-analysis showed that patients with GC with reduced E-cadherin had unfavourable clinicopathological features and poor OS. The pooled ORs of one-, three- and five-year OS were 0.38 (n = 25 studies, 95%CI: 0.25-0.57, Z = 4.61, P < 0.00001), 0.33 (n = 25 studies, 95% CI: 0.23-0.47, Z = 6.22, P < 0.00001), 0.27 (n = 22 studies, 95% CI: 0.18-0.41, Z = 6.23, P < 0.00001), respectively. Moreover, reduced E-cadherin expression significantly correlated with differentiation grade (OR = 0.29, 95% CI: 0.22-0.39, Z = 8.58, P < 0.00001), depth of invasion (OR = 0.49, 95% CI: 0.36-0.66, Z = 4.58, P < 0.00001), lymphatic node metastasis (OR = 0.49, 95% CI: 0.38-0.64, Z = 5.38, P < 0.00001), distant metastasis (OR = 2.24, 95% CI: 1.62-3.09, Z = 4.88, P < 0.00001), peritoneal metastasis (OR = 2.17, 95% CI: 1.39-3.39, Z = 3.40, P = 0.0007), TNM stage (OR = 0.41, 95% CI: 0.28-0.61, Z = 4.44, P < 0.00001), lymphatic vessel invasion (OR = 1.77, 95% CI: 1.11-2.82, Z = 2.39, P = 0.02), vascular invasion (OR = 1.55, 95% CI: 1.22-1.96, Z = 3.58, P = 0.0003), Lauren type (OR = 0.35, 95% CI: 0.21-0.57, Z = 4.14, P < 0.0001), Borrmann classification (OR = 0.50, 95% CI: 0.25-0.99, Z = 1.97, P = 0.048) and tumor size (≥5 cm vs. <5 cm: OR = 1.73, 95% CI: 1.34-2.23, Z = 4.19, P < 0.0001; ≥6 cm vs. <6 cm: OR = 2.29, 95% CI: 1.51-3.49, Z = 3.87, P = 0.0001). No significant association was observed between reduced E-cadherin expression and liver metastasis, perineural invasion, alcohol consumption, smoking status, familial history, Helicobacter pylori (HP) infection. CONCLUSIONS: The reduced expression of E-cadherin is significantly correlated with poor OS and unfavourable clinicopathological features in GC. The expression level of E-cadherin not only serves as a predictor for disease progression and prognosis in GC but also emerges as a novel therapeutic target.

Case Report: Complete Remission of a Patient With Metastatic Gastric Cancer Treated With Nivolumab Combined With Chemotherapy After Palliative Surgery.

Metastatic advanced gastric cancer, for which treatment strategies are extremely limited, has a poor prognosis. Complete remission is rare. Patients usually lose the opportunity of therapeutic surgery because the lesions cannot be completely removed, although it can greatly prolong their survival time. Palliative surgery usually suggests bad outcomes. In recent years, the immune checkpoint inhibitor (ICI) nivolumab has shown significant efficacy in the treatment of advanced gastric cancer. However, its applicable conditions and optimal withdrawal time remain controversial owing to its low response rate and high incidence of immune-related adverse events. Herein, we introduce a 66-year-old male patient with advanced gastric cancer with multiple liver metastases who underwent laparoscopic total gastrectomy for acute gastric bleeding. The patient received eight cycles of S-1 plus oxaliplatin (SOX) and switched to eight cycles of SOX plus nivolumab combined regimen in a stable state, later achieving complete remission. There was no recurrence for 32 months after the surgery. This is the first reported case of gastric cancer with multiple liver metastases with long-term complete remission with nivolumab treatment after palliative surgery. The potential mechanism of complete remission was discussed through clinical, genomic, and immune characteristics. The patient had a history of psoriasis and was positive for programmed death ligand 1 (PD-L1), and the interaction of TP53 mutation and HER-2 (-) gene may be associated with complete remission.

Immune-related keratitis is a rare complication associated with nivolumab treatment in a patient with advanced colorectal cancer: A case report.

Background: Immunotherapy has been widely used to treat Colorectal cancer but has also observe some immune-related adverse effects. With proper treatment, most irAE can be solved and the effect of immunotherapy will not be affected by temporary immunosuppression. However, there are few reports about corneal irAE, and the current understanding of irAE is incomplete. Here we report a metastatic colorectal cancer case of immune-related keratitis caused by nivolumab and to explore the occurrence of immune-related keratitis. Case description: Here we report the case of a 49-year-old man with mCRC who had no previous ocular disease but developed immune-related ulcerative keratitis after treatment with nivolumab. We summarize a large amount of literature to discuss the mechanism of immune-related keratitis. In addition, we conclude a method that may be used to detect the occurrence of immune keratitis, by monitoring MMPs and maspin in patients treated with nivolumab. We believe immune-related keratitis may be a rare complication of nivolumab in the treatment of mCRC. The effect of simple anti-infective therapy and repair-promoting drugs was not obvious, but the effect of glucocorticoid combined with autologous serum was significant. Conclusion: The mechanism of immune-related keratitis is that nivolumab destroys the immune microenvironment and ACAID, and affects corneal healing. Patients who use nivolumab can prevent immune keratitis by testing MMPs and maspin. The occurrence of immune keratitis may be a good indicator of the efficacy of ICI, and further study can be done in the follow-up.

Patient-Derived Organoid Facilitating Personalized Medicine in Gastrointestinal Stromal Tumor With Liver Metastasis: A Case Report.

The gastrointestinal stromal tumors (GIST) are a rare gastrointestinal tract malignancy. The two primary mutation sites are found in KIT and platelet-derived growth factor receptor-α (PDGFR-α) genes. The current study reports on a point mutation within the exon 11 of KIT, named KIT p.V560E. Patient-derived organoids (PDOs) are potential 3D in vitro models of tissues that can be used to identify sensitivity toward specific targets in patients with tumors and allow for personalized medicine when drugs specific for newly identified genetic locus mutations are not yet available. This study describes a 68-year-old patient who complained of diffused abdominal pain and intermittent melena lasting more than 10 days. He has no other gastrointestinal abnormalities, prior abdominal surgery, or related family history. Surgery was conducted first to remove the lesions and ascertain the disease through histology and immunohistochemical stains of the mass. Immunohistochemistry revealed that the tumor was positive for CD117 and Dog-1. Based on the above findings, he was diagnosed with GISTs. Gene detection analysis and organoid culture were then performed to verify clinical decisions. KIT p.V560E and the reduced number of RB1 copies were identified as two obvious mutations, so the patient was administrated first-line treatment of imatinib 400 mg/d. However, progressive disease prompted us to switch to sunitinib, and his condition gradually improved. Meanwhile, organoid culture showed sensitivity to sunitinib and tolerance to imatinib with half-maximal inhibitory concentration (IC50) values of 0.89 and >20, respectively. In summary, to the best of our knowledge, this is the first time that the established organoid culture indicated that the GISTs organoid could identify the sensitivity to target therapies and facilitate individual-based treatment.

Quantitative detection of circulating MT-ND1 as a potential biomarker for colorectal cancer.

Liquid biopsy represents a diagnostic and monitoring tool and the circulating cell-free mitochondrial DNA (mtDNA) plays a vital role in tumor diagnosis and dynamic assessment. Colorectal cancer (CRC) is one of the most common fatal cancers worldwide. Mitochondrially encoded NADH dehydrogenase subunit 1 (MT-ND1) encodes the biggest subunit of respiratory complex I of mtDNA, and mutations in the MT-ND1 are common in CRC. We sought to determine if mutations in circulating MT-ND1 could be a potential biomarker for colorectal cancer. In this study, twenty-two CRC patients at Zhujiang Hospital were included. We mainly used droplet digital PCR to determine the mutation status of MT-ND1, combined with clinical data. In the experiment in vivo, cell-free mtDNA generally presented high concordance with tumor tissues. By quantitative PCR, the MT-ND1 content of plasma in CRC patients was significantly higher than that in healthy individuals (58.01 vs. 0.64, p=0.027). The detection of circulating MT-ND1 content and variants (m.3606 A>G, m.3970 C>T, m.4071 C>T, m.4086 C>T) in cfDNA showed a good correlation with predicted tumor response and progression to chemotherapy. In conclusion, the content and variants of circulating MT-ND1 may become a versatile tool for the diagnosis and monitoring of colorectal cancer.

Differences in the dielectric properties of various benign and malignant thyroid nodules.

PURPOSE: This experiment was conducted to investigate the dielectric properties of different types of thyroid nodules. Our goal was to find a simple and fast method to detect thyroid diseases at different stages from the dielectric properties of thyroid nodules. METHODS: We used the open-ended coaxial line method to measure the dielectric permittivities of thyroid tissues from 155 patients at frequencies ranging from 1 to 4000 MHz. Tissues that were investigated included normal thyroid tissue and benign and malignant thyroid nodules (nodular goiter, follicular adenoma, papillary carcinoma, and follicular carcinoma), as determined from pathological reports. Differences in dielectric properties were measured between each nodule and the surrounding 1 cm of tissue. RESULTS: The analysis results revealed that the dielectric permittivity and conductivity values were positively correlated with the degree of malignancy of the nodule (normal < benign < malignant; all differences P < 0.05). This was more obvious at frequencies within 20~70 MHz, following the order normal tissue < nodular goiter < follicular adenoma < papillary carcinoma < follicular carcinoma. A significant difference (P < 0.05) in dielectric permittivity and conductivity was found when comparing these nodules with the surrounding 1 cm of tissue. CONCLUSIONS: Normal, benign, and malignant nodules were successfully distinguished from one another, and dielectric permittivity was found to be a more sensitive parameter than conductivity. In particular, different disease types can be distinguished at a stimulation frequency of 20~70 MHz, which shows that dielectric properties have application prospects for the detection and diagnosis of cancer. At the same time, the dielectric parameter differences between the surrounding 1 cm of tissue and the diseased nodule can distinguish the tumor and its surrounding tissues in real time during surgery to determine the tumor boundary.

Prognostic impact of preoperative prognostic nutritional index in resected advanced gastric cancer: A multicenter propensity score analysis.

BACKGROUND: Advanced gastric cancer (AGC) causes debilitating malnutrition and leads to deterioration of the immune response. However, the concept of the prognostic nutritional index (PNI) is controversial when applied to patients with AGC. The aim of the present study was to evaluate the effect of the PNI after gastrectomy in patients with AGC. MATERIALS AND METHODS: A multicenter retrospective study was conducted using propensity score matching (PSM) in gastric adenocarcinoma patients who underwent resection via laparoscopic or open surgery between 2014 and 2017. To overcome selection bias, we performed 1:1 matching using 5 covariates. RESULTS: The resection margins (P < 0.001) and LNM (P = 0.004) were significantly different between the two groups. In univariate analysis, poor tumor differentiation (P = 0.038) (R1+R2, P = 0.004), vascular and neural invasion (P < 0.001), and a PNI<50 (P < 0.001) were associated with poor recurrence-free survival (RFS). In multivariate analysis, a PNI<50 (hazard ratio (HR), 12.993; P < 0.001) was a risk factor for RFS. Univariate analysis for overall survival (OS) revealed that a PNI<50 (P < 0.001) (R1+R2,P = 0.006) and vascular and neural invasion (P < 0.001) were risk factors. In subsequent multivariate analysis, a PNI<50 (HR, 24.501; P < 0.001) was a significant risk factor for OS. Clinical assessments performed during a 12.34 (±5.050) month follow-up revealed that OS (P < 0.001) and RFS (P < 0.001) were worse in patients with a low PNI (<50) than in matched patients with a high PNI. CONCLUSION: A low PNI is a strong predictor of unfavorable RFS and OS in patients with AGC.

The analysis of clinicopathologic predictors of lymph node metastasis and postoperative recurrence in patients with papillary thyroid microcarcinoma from Guangdong Province, China-a multicenter retrospective study.

PURPOSE: Currently the extent of lymph node dissection (LND) for papillary thyroid microcarcinoma (PTMC) remains controversial. The present study aims to investigate the clinicopathologic predictors of lymph node metastasis (LNM) and prognosis in PTMC patients from Guangdong to enable appropriate treatment and follow-up. METHODS: Data including demographics, tumor size, multifocality, extrathyroidal extension (ETE) and concomitant thyroiditis were collected from 374 untreated PTMC patients from Guangdong, China. Univariate and multivariate analyses were performed to identify clinicopathologic predictors of LNM and prognostic indicators in PTMC patients with LNM. RESULTS: During the follow-up period of 120 months, recurrence was significantly higher in patients with LNM than in patients without LNM (P<0.05). Age <45 years, larger tumor (>5 mm) and multifocality were predictors of LNM; age <45 years, larger tumor size and absence of concomitant thyroiditis were associated with central LNM (CLNM); male sex, ETE and multifocality were correlated with lateral LNM (LLNM) (P<0.05). There was no difference in recurrence between patients with CLNM and LLNM (P>0.05). LNM in PTMC primarily influenced disease-free survival. Age >45 years and male sex were risk factors of recurrence in PTMC patients with LNM. Male patients with CLNM and older patients with LLNM exhibited worse prognosis (P<0.05). CONCLUSIONS: PTMC easily metastasizes to cervical lymph nodes, which significantly influences prognosis. Prophylactic LND is recommended in PTMC patients from Guangdong, China, who have a high risk of CLNM and/or LLNM. More aggressive postoperative treatment and more frequent follow-up could be considered for older and/or male PTMC patients with LNM.

A genome-wide assessment of variations of primary colorectal cancer maintained in metastases.

Colorectal cancer (CRC) is a highly heterogeneous disease that is the third leading cause of cancer-related deaths worldwide. This study presents a genome-wide assessment of variations in primary colorectal cancer maintained in metastases, even in distant metastases. The purpose of this study was to determine whether intratumor heterogeneity is related to disease progression and metastasis in CRC. The results showed that 882 single nucleotide polymorphism (SNP) associated genes and 473 copy number variant (CNV) associated genes specific to metastasis were found. In addition, 57 SNPs mapped to miRNAs showed significant differences between primary tumors and metastases. Functional annotation of metastasis-specific genes suggested that adhesion and immune regulation may be essential in the development of tumors. Moreover, the locus rs12881063 in the fourteenth chromosome was found to have a high rate of the G/C type in metastases. The rate of the G/C type in nearby lymph node metastases was 66.7%, while the rate of the G/C type in distance lymph node metastases was 83.3%. These results indicate that rs12881063 may be the basis for clinical diagnosis of CRC metastasis.

The prognostic value of regional lymph node metastases in patients of Guangdong Province, China with differentiated thyroid cancer: A multicenter retrospective clinical study.

Although the prognostic value of nodal metastases in differentiated thyroid cancer remains controversial, it is of interest to evaluate and understand the different characteristics of predictive outcomes.A multicenter retrospective study was conducted in 215 untreated patients with differentiated thyroid cancer from July 1997 to July 2015 in 4 medical centers of Guangdong Province. A total of 107 patients with nodal metastases (group A) were compared to 108 patients without metastases (group B). The 5-year disease-free survival (DFS), overall survival (OS), and postoperative complications in both groups were calculated. Variables predictive of DFS and OS were evaluated in group A.The group A had lower 5-year DFS (69.16%, 11 months) and shorter median time of recurrence than those in group B (87.96%, 8.5 months, respectively, P < 0.001). The incidence of temporary hypoparathyroidism in group A is lower; whereas higher incidence of temporary unilateral vocal cord palsy, permanent hypoparathyroidism, permanent unilateral vocal cord palsy, and bilateral vocal cord palsy in group A were observed. Both univariate and multivariate analyses in group A revealed that age, pathological tumor node metastasis (pTNM) stage, and histology were related to DFS (P < 0.05); while pTNM stage and histology were related to OS only in univariate analyses.Positive nodal metastases have significant prognostic value in patients with differentiated thyroid cancer in Guangdong, China and primarily reduce DFS. Moreover, patients with positive nodal metastases who are >45 years and have higher pTNM stage or follicular histology tend to have poor prognosis. Selective lymph node dissection with appropriate postoperative treatment and frequent follow-up should be accorded to these vulnerable groups of patients.

Anti-Warburg effect of rosmarinic acid via miR-155 in gastric cancer cells.

BACKGROUND: The Warburg effect refers to glycolytic production of adenosine triphosphate under aerobic conditions, and is a universal property of most cancer cells. Chronic inflammation is a key factor promoting the Warburg effect. This study aimed to determine whether rosmarinic acid (RA) has an anti-Warburg effect in gastric carcinoma in vitro and in vivo. The mechanism for the anti-Warburg effect was also investigated. METHODS: An MTT assay was used to examine MKN45 cell growth in vitro. An enzyme-linked immunosorbent assay was used to detect proinflammatory cytokines. Real-time polymerase chain reaction was used to evaluate levels of microRNA expression in cells. Protein expression was determined by Western blotting assay. Mouse xenograft models were established using MKN45 cells to assess the anti-Warburg effect in gastric carcinoma in vivo. RESULTS: RA suppressed glucose uptake and lactate production. It also inhibited expression of transcription factor hypoxia-inducible factor-1α, which affects the glycolytic pathway. Inflammation promoted the Warburg effect in cancer cells. As expected, RA inhibited proinflammatory cytokines and microRNAs related to inflammation, suggesting that RA may suppress the Warburg effect via an inflammatory pathway, such as that involving interleukin (IL)-6/signal transducer and activator of transcription-3 (STAT3). miR-155 was found to be an important mediator in the relationship between inflammation and tumorigenesis. We further showed that miR-155 was the target gene regulating the Warburg effect via inactivation of the IL-6/STAT3 pathway. Moreover, we found that RA suppressed the Warburg effect in vivo. CONCLUSION: RA might potentially be a therapeutic agent for suppressing the Warburg effect in gastric carcinoma.

Comparison of a New High-Frequency Electric Welding System for Intestinal Closure with Hand-Sewn In Vivo Pig Model.

BACKGROUND: Various surgical small intestinal anastomosis methods are in current use, but improvements are always desired. Thus, we compared the feasibility, effectiveness, and safety of a new high-frequency electric welding (HFEW) system for sealing the small bowel versus a hand-sewn in vivo pig model. MATERIALS AND METHODS: The 96 bowel segments of three pigs were randomized to be sutured either by the HFEW-300 PATONMED device (E.O. Paton Electric Welding Institute of the National Academy of Sciences of Ukraine, Kiev, Ukraine) or hand-sewn, and mucosa-to-mucosa fusions were subjected in vivo testing in the pigs. Bursting pressures, suture time, thermal damage, and the temperature of sealed ends were measured. RESULTS: Segments that had been treated with a hand-sutured ligature or double-sealed with HFEW were compared. Burst pressure was significantly higher in the hand-sutured group than in the HFEW group (136.2 mm Hg versus 75.8 mm Hg, P<.01). All 48 pig small bowels closed by the HFEW-300 generator showed a success rate of 100.0%. The closing time in the HFEW group was significantly shorter (P<.01). The pathological changes of the closed ends were mainly presented as acute thermal- and pressure-induced injuries. CONCLUSIONS: Outcomes of the current in vivo study suggest that HFEW is an effective and safe method for ligation of the small bowel in pigs.

[Screening molecular markers in early breast cancer of the same pathological types but with different prognoses using Agilent gene chip].

OBJECTIVE: To screen molecular markers in early breast cancer and establish gene subtyping-based diagnostic criteria for predicting the prognosis of early breast cancers. METHODS: Tumor tissue specimens were obtained from 8 patients with early breast cancer for analysis of the differentially expressed genes using Agilent custom 8×15 000 chips in combination with the prognostic data of the patients. Another 42 tumor tissue specimens were used to validate the differential genes by real-time fluorescent quantitative PCR. RESULTS: Gene microarray analysis identified 132 differentially expressed genes between the patients with favorable and poor prognosis, and 44 of these genes were significantly up-regulated (by over two folds) and 88 down-regulated in patients with poor prognoses. CONCLUSION: The gene expression profiles differ in early breast cancer tissues of the same pathological type but with different clinical stages and prognoses, and CD44, MKI67, NTRK2, Nek2, C16orf60, TOP2A, ANCCA, and RRM2 genes can be used as the prognostic markers for early breast cancer.