Feasibility and safety of laparoscopic radical cystectomy for male octogenarians with muscle-invasive bladder cancer.

This study was designed to evaluate the safety and feasibility of laparoscopic radical cystectomy (LRC) for male octogenarian patients with muscle-invasive bladder cancer (MIBC). Briefly, a total of 57 male octogenarian patients (A group) with bladder carcinoma were enrolled and underwent LRC and intracorporeal pelvic lymph node dissection with bilateral cutaneous ureterostomy from May 2016 to December 2022. Besides, 63 male patients (age < 80 years old) with bladder carcinoma undergoing LRC and 17 octogenarian male patients with bladder carcinoma undergoing open radical cystectomy (ORC) were enrolled in B and C groups as control. All perioperative clinical materials and outcomes of long-term follow-up, and complication were collected. The specific results were shown as follows. Compared with C group, the operation time and resected lymph node in A group was increased, and the estimated blood loss, the number of transfusion needed, duration of pelvic drainage and hospital stay after surgery was decreased. The death rate and ileus complication rate were higher in A group (12 cases) than in C group (15 cases). The cases of ureteral stricture in A group (13 cases) was decreased compared with that in C group. Overall, LRC and bilateral cutaneous ureterostomy are safe, feasible and better choices for the treatment of male octogenarian patients with MIBC. The octogenarian receiving cutaneous ureterostomy heals slowly and exists certain incomplete intestinal obstruction after surgery.

Dynamic behavior of a zero-group velocity guided mode in rail structures.

Important characteristics of a zero-group velocity (ZGV) mode in a standard rail are investigated through numerical simulation and experiment. First, the semi-analytical finite element analysis is implemented to compute dispersion curves for the rail structure and the first ZGV point is identified. Backward waves are identified through opposing senses of group and phase velocities. Next, a time-dependent finite element model is used to understand the dynamic response of the rail. Finally, experimental measurements confirm that ZGV modes in rail structures are formed through interferences between two opposite-traveling waves, which is analogous to the S1-S2b ZGV Lamb mode in plate structures.

Exercise improves subchondral bone microenvironment through regulating bone-cartilage crosstalk.

Articular cartilage degeneration has been proved to cause a variety of joint diseases, among which osteoarthritis is the most typical. Osteoarthritis is characterized by articular cartilage degeneration and persistent pain, which affects the quality of life of patients as well as brings a heavy burden to society. The occurrence and development of osteoarthritis is related to the disorder of the subchondral bone microenvironment. Appropriate exercise can improve the subchondral bone microenvironment, thus playing an essential role in preventing and treating osteoarthritis. However, the exact mechanism whereby exercise improves the subchondral bone microenvironment remains unclear. There is biomechanical interaction as well as biochemical crosstalk between bone and cartilage. And the crosstalk between bone and cartilage is the key to bone-cartilage homeostasis maintenance. From the perspective of biomechanical and biochemical crosstalk between bone and cartilage, this paper reviews the effects of exercise-mediated bone-cartilage crosstalk on the subchondral bone microenvironment, aiming to provide a theoretical basis for the prevention and treatment of degenerative bone diseases.

Extraction and selective promotion of zero-group velocity and cutoff frequency resonances in bi-dimensional waveguides using the electromechanical impedance method.

This study showcases the electromechanical impedance (EMI) technique for extracting and promoting zero-group velocity (ZGV) and cutoff frequency resonances in a waveguide structure. We identify the mechanisms of multiple resonances in the EMI spectra via a wave propagation perspective. Both simulation and experiments reveal the fact that sharp resonances in the conductance spectra are associated with either ZGV or cutoff frequency points. Consequently, we design four test configurations to enhance local resonances by aligning induced motions with considered mode shapes. Reasonable agreement between simulation and experiment results is observed. We evaluate the performance of considered configurations in terms of mode enhancement, and configurations that can selectively promote certain mode families are summarized. This study also shines the light on the EMI technique for quantitative non-destructive evaluation (NDE) by potentially supporting the inverse characterization of mechanical properties of host structures.

Imaging features of primary mucinous adenocarcinoma of bladder outlet and urethra: a case report and literature review.

Background: Primary bladder adenocarcinoma (PBA) only accounts for 2% of primary bladder cancers. PBA symptoms vary according to the volume, location, and the metastasis of the tumor. The most common symptoms include suprapubic pain, hematuria, dysuria, and bladder irritation. In the initial stage, the diagnosis of PBA is possibly delayed due to the lack of obvious symptoms. When diagnosed, up to 40% of patients are reported to have metastatic disease. PBA can occur anywhere in the bladder, especially the bottom, neck, and roof. However, the mass at the bladder outlet and urethra is a rare presentation of PBA. Through this rare case, when clinicians encounter similar patients, they can have richer ideas for diagnosis and treatment, which is helpful for the timely diagnosis and effective treatment. Case Description: A 62-year-old female was referred to an outpatient urology surgery service due to a 1-year history of narrowing of the urinary route and difficulties in urination. No significant abnormalities were found in other surgical examinations, and the patient denied having a genetic history or similar history in her family. Ultrasonography revealed a hypoechoic mass of 6.5 cm × 3.8 cm × 4.4 cm at the bladder outlet and urethra. Computed tomography (CT) plain scan and enhancing scan displayed that the wall of bladder was thickened, and soft tissue density was seen at the bladder outlet and urethra with slight enhancement and an unclear partial boundary. The mass was confirmed to be PBA. Conclusions: Primary mucinous adenocarcinoma of bladder usually detected in the posterior wall and trigone, but at the bladder outlet and urethra was rare. In this report, Imaging examination showed that the mass was located at the bladder outlet and urethra, and was finally confirmed by surgery. Due to the location of the growth, our patient's only symptoms were dysuria and urinary tract thinning, without hematuria, suprapubic pain, or bladder irritation. Timely diagnosis and treatment of this case depend on the findings of imaging examination. We describe the imaging features of this rare disease entity and the relevant literature review.

The correlation analysis of TERT promoter mutations with IDH1/2 mutations and 1p/19q detected in human gliomas.

BACKGROUND: To investigate the correlations between mutations in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase (IDH) 1 and 2 mutations or 1p/19q deletion in human gliomas. METHODS: TERT promoter gene and IDH gene mutations in 110 glioma specimens were evaluated using first generation Sanger sequencing. The 1p/19q status was determined with fluorescence in situ hybridization. The relationship between TERT promoter mutations and IDH gene mutations as well as 1p/19q deletion was analyzed using the χ2 test and Spearman rank correlation test. RESULTS: The TERT promoter mutation rate in 110 glioma specimens was 39.09% (43/110), with a rate of 32.56% (14/43) for C228T mutation and 67.44% (29/43) for C250T mutation. The IDH gene mutation rate in all specimens was 31.82% (35/110), with a rate of 52.78% (19/36) in low-grade gliomas and 21.62% (16/74) in high grade gliomas. The 1p/19q deletion rate was 28.18% (31/110) in all specimens. Correlation analysis revealed that TERT promoter mutation was positively correlated with 1p/19q deletion (relative precision (rp) = 0.244, P = .015). In lower-grade glioma with IDH mutation, TERT promoter mutation was positively correlated with 1p/19q deletion (rp = 0.856, P = .000). The prognosis for gliomas with IDH mutation/TERT mutation/1p/19qdeletion was good. Mutation of the TERT promoter was negatively correlated with IDH gene mutation (rp = -0.290, P = .004), except in 10 cases of oligodendroglioma and 1 case of anaplastic oligodendroglioma. CONCLUSION: There may be a complex inter-regulatory relationship between the mutations of the TERT promoter and IDH gene as well as 1p/19q abnormalities in human gliomas.

A retrospective analysis on the effect of single-channel minimally invasive percutaneous nephrolithotomy combined with retrograde flexible ureteroscopy using the completely lateral decubitus and semi-lithotomy positions to treat complex kidney stones.

BACKGROUND: Some types of complex kidney stones cannot be broken down and removed through single-channel percutaneous nephroscope or retrograde flexible ureteroscope. In order to be removed, these types of stones require multiple combined methods to be performed. The aim of this study was to retrospectively evaluate the clinical effect of single-channel minimally invasive percutaneous nephrolithotomy (mPCNL) combined with retrograde flexible ureteroscopy using the completely lateral decubitus and semi-lithotomy positions for treating complex renal calculi. METHODS: We selected 117 patients with complex renal calculi who were admitted to Peking University Shougang Hospital and Weifang People's Hospital from January 1, 2017, to January 31, 2021. All patients were treated with single-channel mPCNL combined with retrograde flexible ureteroscopy in the completely lateral decubitus and semi-lithotomy positions. During the operation, the patients were placed in a completely lateral decubitus position, or their lower limbs were placed in a semi-lithotomy position for a single attempt only. RESULTS: An 18-Fr percutaneous channel was successfully established in all patients. The mean operation time was 112±37 minutes, and the average blood loss was 71±31 mL. A 14-Fr renal fistula was maintained for 7 days, a urethral catheter for 2-3 days, and a ureteral stent tube for 2 weeks after each surgery. According to the results of computed tomography (CT) scans performed 3-5 days after the operation, the total lithotripsy success rate reached 100%, with a first-stage lithotripsy rate of 98.29%. Two patients were found to each have 1 residual stone, with a diameter of 4 mm, left in kidney by CT, which then was to be removed under local anesthesia. The average postoperative hospitalized time was 7±2 days, and no severe complications occurred perioperatively. CONCLUSIONS: Single-channel mPCNL combined with retrograde flexible ureteroscopy in the completely lateral decubitus and semi-lithotomy positions is a safe, feasible, and highly effective method of treating complex renal calculi, which is of benefit to save operation time and facilitate operation process, because patient's position could not need to be changed repeatedly during the surgery.

Hydrogen-saturated saline mediated neuroprotection through autophagy via PI3K/AKT/mTOR pathway in early and medium stages of rotenone-induced Parkinson's disease rats.

Some cardiovascular symptoms in the early stage of Parkinson's disease (PD) were related to degeneration of the rostral ventrolateral medulla (RVLM) catecholaminergic neurons. To date, little is known about the effects of hydrogen water on early stage of PD. Here, protective actions of hydrogen-saturated saline (HS) on rotenone-induced PD rats, as well as its underlying mechanisms were investigated. HS was used to treat PD rats at three general stages; early, medium and late, which were represented by rotenone induced rats for 0, 7 and 14 days. HS treatment significantly alleviated the cardiovascular and motor symptoms in rotenone-induced PD rats, improved the survival number of RVLM catecholaminergic neurons and nigral dopamine neurons only in early and medium stages of PD rats. Decreased levels of reactive oxygen species (ROS) and alpha-synuclein (α-Syn), transformation of microtubule associated protein 1 light chain 3 (LC3)-I/II and degradation of sequestosome 1 (p62) were detected, as well as increased expression level of autophagy related protein 5 (ATG5) and B-cell lymphoma-2 interacting protein 1 (Beclin-1) in the RVLM and substantia nigra (SN) after HS treatment in early and medium stages of PD rats. In addition, phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) and mammalian rapamycin target protein (mTOR) decreased after HS treatment in early and medium stages of PD rats. The results suggested that HS treatment exerted beneficial effects in early and medium stages before motor impairments emerged but not in the late stage of rotenone-induced PD rats. It exerted neuroprotection with RVLM catecholaminergic neurons and nigral dopamine neurons, mediated in part by decreasing levels of ROS and α-Syn through increasing autophagy machinery which were partly via inhibiting PI3K-Akt-mTOR pathway.

MicroRNA-10a suppresses cell metastasis by targeting BDNF and predicted patients survival in renal cell carcinoma.

PURPOSE: Renal cell carcinoma (RCC) is the most common renal neoplasm and accounts for 3% of all cancers. Increasing studies reported that miR-10a, acting as tumor suppressor, was downregulated in several cancers. It has been reported that the proteins encoded by Brain-Derived Neutrophic Factor (BDNF) were members of the nerve growth factor family, and could promote neuronal survival in the adult brain. The purpose of this study was to explore how miR-10a worked in RCC on the metastasis. METHODS: The expression level of miR-10a and BDNF were calculated using RT-PCR and western blot. Transwell assay was utilized to evaluate the invasive ability. Kaplan-Meier method along with log-rank test were applied to evaluate the 5-year overall survival of RCC patients. RESULTS: miR-10a was significantly downregulated and BDNF was upregulated in RCC tissues and cell lines A498 and 786-O. The expression of miR-10a had a reverse correlation with BDNF in RCC tissues. Overexpression of miR-10a or interference of BDNF inhibited the invasion and epithelial-mesenchymal transition (EMT) of A498 cells. What's more, BDNF was demonstrated to be a target gene of miR-10a and miR-10a could mediate the expression of BDNF in RCC. In addition, low expression of miR-10a or overexpression of BDNF predicted poor prognosis of RCC patients. CONCLUSION: Our results indicated that miR-10a inhibited the invasion and EMT by regulating BDNF in RCC. The newly identified miR-10a/BDNF axis provides novel insight into the pathogenesis of RCC.

Impact of the updated 2018 ASCO/CAP guidelines on HER2 FISH testing in invasive breast cancer: a retrospective study of HER2 fish results of 2233 cases.

OBJECTIVES: Human epidermal growth factor receptor 2 (HER2, ERBB2) is a valuable prognostic and predictive biomarker in breast cancer. Accurate assessment of HER2 status is essential in selecting the patients with invasive breast cancer who will likely response to HER2-targeted therapies. Some major modifications in the diagnostic recommendation for fluorescence in situ hybridization (FISH) have been made in the updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guideline. According to the revised guideline, concomitant IHC assays are required to arrive at the most accurate HER2 status designation after HER2 FISH equivocal results; however, little is known about its influence on the clinical practice of pathologist. The purpose of this study was to evaluate the impact of the revised 2018 ASCO/CAP guidelines on the HER2 status designation. METHODS: We retrospectively reviewed the HER2 FISH testing results from 2233 cases of invasive breast cancer between January 2014 and December 2017. Concomitant immunohistochemistry (IHC) were performed on the same tissue blocks that were used for the FISH testing. RESULTS: Compared to the 2013 guidelines, the HER2 status in 183 (8.2%) cases were re-defined when reassessed by the 2018 guidelines. Among these 183 cases, 175 equivocal cases according to the 2013 guideline were re-defined as HER2 negative (n = 173) or HER2 positive (n = 2). Eight previously classified as HER2 positive cases were converted to negative in the 2018 scheme, all of which were with HER2 IHC scores of 1+ or 2+. The number of cases in the negative category was 1705 according to the 2018 guidelines as opposed to 1524 by the 2013 guidelines. CONCLUSIONS: The updated 2018 ASCO/CAP guidelines eliminated the FISH equivocal category, which can be attributed to reflex HER2 IHC, and partly ease the dilemma for clinical practice. Reflex IHC for FISH equivocal cases is of prime importance; furthermore, HER2 FISH results were converted from positivity to negativity based on the concomitant IHC results in a small percentage of cases. In all, implementation of the 2018 ASCO/CAP guidelines provides much clearer instructions and recommendations for the HER2 status designation, and thus reduces the risk of misdiagnosis.

Involment of RAS/ERK1/2 signaling and MEF2C in miR-155-3p inhibition-triggered cardiomyocyte differentiation of embryonic stem cell.

MicroRNAs (miRNAs) are short, noncoding RNAs that regulate post-transcriptional gene expression by targeting messenger RNAs (mRNAs) for cleavage or translational repression. Growing evidence indicates that miR-155 expression changes with the development of heart and plays an important role in heart physiopathology. However, the role of miR-155 in cardiac cells differentiation is unclear. Using the well-established embryonic stem cell (ESC), we demonstrated that miR-155-3p expression was down-regulated during cardiogenesis from mouse ESC. By contrast, the myogenic enhance factor 2C (MEF2C), a predicted target gene of miR-155-3p, was up-regulated. We further demonstrated that miR-155-3p inhibition increased the percentage of embryoid bodies (EB) beating and up-regulated the expression of cardiac specific markers, GATA4, Nkx2.5, and cTnT mRNA and protein. Notably, miR-155-3p inhibition caused upregulation of MEF2C, KRAS and ERK1/2. ERK1/2 inhibitor, PD98059 significantly decreased the expression of MEF2C protein. These findings indicate that miR-155-3p inhibition promotes cardiogenesis, and its mechanisms are involved in the RAS-ERK1/2 signaling and MEF2C.

Impact of repeat HER2 testing after initial equivocal HER2 FISH results using 2013 ASCO/CAP guidelines.

PURPOSE: The updated 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing have made some major changes in HER2 fluorescence in situ hybridization (FISH) interpretation criteria with additional FISH equivocal cases. Repeat HER2 testing is recommended after initial HER2 FISH equivocal results; however, little is known about its impact on final HER2 status. The aim of this study is to investigate whether reflex test clarifies HER2 status, and to characterize clinicopathological features of the newly defined HER2 equivocal group. METHODS: A total of 886 consecutive cases of primary invasive breast cancer conducted with dual-probe HER2 FISH testing between November 2013 and December 2015 were reviewed. HER2 immunohistochemistry (IHC) and FISH testing were performed on a different tissue block or a new specimen after initial HER2 FISH equivocal results. RESULTS: Compared to 2007 guideline, 85 (9.6%) cases changed their category by using 2013 guideline. The major change of the 85 cases is that 57 (6.4%) cases in HER2 FISH-negative category changed to equivocal, and the equivocal category cases increased from 36 to 67. HER2 FISH equivocal was significantly associated with HER2 IHC equivocal (2+) and chromosome 17 polysomy (P < 0.01). Repeat testing by IHC and FISH clarified HER2 status in 33 and 42% of HER2 equivocal cases, respectively. Overall 32 (48%) initial HER2 equivocal cases stayed HER2 equivocal after repeat FISH and or IHC testing. These tumors were ER/PR+, with high KI-67 index. CONCLUSION: New guidelines classify more HER2 FISH equivocal cases. Repeat HER2 testing clarifies HER2 status in about 50% of initial HER2 FISH equivocal cases. In addition, HER2 equivocal cases merit further study as there is limited information about prognosis and optimal treatment strategy for this population.

Investigation of correlation between mutational status in key EGFR signaling genes and prognosis of stage II colorectal cancer.

AIM: To investigate the relationship between mutations of key genes in the EGFR signaling pathway and the prognosis of stage II colorectal cancer patients without chemotherapy. MATERIALS & METHODS: The incidence of KRAS, NRAS, BRAF, PIK3CA mutations and deficient DNA mismatch repair were assessed in 160 stage II colorectal cancer patients who had been treated by radical operation without adjuvant chemotherapy. RESULTS: Mutations in KRAS, BRAF or PIK3CA were associated with poor prognosis, while the deficient DNA mismatch repair status was not associated with the prognosis. Combining these three markers, the sensitivity of the predicted value for poor progression-free survival and overall survival reached 0.645 (p = 0.002) and 0.709 (p = 0.001), respectively. CONCLUSION: Knowing the mutation status of KRAS, BRAF or PIK3CA in stage II colorectal cancer can significantly improve the accuracy of prognoses.

Theoretical Analysis of the Dynamic Properties of a 2-2 Cement-Based Piezoelectric Dual-Layer Stacked Sensor under Impact Load.

Cement-based piezoelectric materials are widely used due to the fact that compared with common smart materials, they overcome the defects of structure-incompatibility and frequency inconsistency with a concrete structure. However, the present understanding of the mechanical behavior of cement-based piezoelectric smart materials under impact load is still limited. The dynamic characteristics under impact load are of importance, for example, for studying the anti-collision properties of engineering structures and aircraft takeoff-landing safety. Therefore, in this paper, an analytical model was proposed to investigate the dynamic properties of a 2-2 cement-based piezoelectric dual-layer stacked sensor under impact load based on the piezoelectric effect. Theoretical solutions are obtained by utilizing the variable separation and Duhamel integral method. To simulate the impact load and verify the theory, three types of loads, including atransient step load, isosceles triangle load and haversine wave load, are considered and the comparisons between the theoretical results, Li's results and numerical results are presented by using the control variate method and good agreement is found. Furthermore, the influences of several parameters were discussed and other conclusions about this sensor are also given. This should prove very helpful for the design and optimization of the 2-2 cement-based piezoelectric dual-layer stacked sensor in engineering.

Impact Mechanical Response of a 2-2 Cement-Based Piezoelectric Sensor Considering the Electrode Layer Effect.

Cement-based piezoelectric composite, has been widely used as a kind of smart material in structural health monitoring and active vibration control. However, transient dynamic loads such as impact loads may cause serious damage to the composite. Considering the electrode layer effect, this paper aimed to investigate the theoretical response of a 2-2 cement-based piezoelectric composite sensor subjected to an impact load. The vibration behaviors are analyzed by using the mode summation method and the virtual work principle. To simulate the impact load, transient haversine wave loads are assumed in the numerical simulation. Close agreements between theoretical and numerical solutions are found for peak transient haversine wave loads larger than 500 kPa, therefore proving the validity of the theory. Moreover, the influence of the electrode material and geometrical parameters on the dynamic characteristics of this sensor are considered. The present work should be beneficial to the design of this kind of sensor by taking into account the electrode layer effect.

PIK3R1 targeting by miR-21 suppresses tumor cell migration and invasion by reducing PI3K/AKT signaling and reversing EMT, and predicts clinical outcome of breast cancer.

We have previously shown that dysregulation of miR-21 functioned as an oncomiR in breast cancer. The aim of the present study was to elucidate the mechanisms by which miR-21 regulate breast tumor migration and invasion. We applied pathway analysis on genome microarray data and target-predicting algorithms for miR-21 target screening, and used luciferase reporting assay to confirm the direct target. Thereafter, we investigated the function of the target gene phosphoinositide-3-kinase, regulatory subunit 1 (α) (PIK3R1), and detected PIK3R1 coding protein (p85α) by immunohistochemistry and miR-21 by RT-qPCR on 320 archival paraffin-embedded tissues of breast cancer to evaluate the correlation of their expression with prognosis. First, we found that PIK3R1 suppressed growth, invasiveness, and metastatic properties of breast cancer cells. Next, we identified the PIK3R1 as a direct target of miR-21 and showed that it was negatively regulated by miR-21. Furthermore, we demonstrated that p85α overexpression phenocopied the suppression effects of antimiR-21 on breast cancer cell growth, migration and invasion, indicating its tumor suppressor role in breast cancer. On the contrary, PIK3R1 knockdown abrogated antimiR­21-induced effect on breast cancer cells. Notably, antimiR-21 induction increased p85α, accompanied by decreased p-AKT level. Besides, antimiR-21/PIK3R1-induced suppression of invasiveness in breast cancer cells was mediated by reversing epithelial-mesenchymal transition (EMT). p85α downregulation was found in 25 (7.8%) of the 320 breast cancer patients, and was associated with inferior 5-year disease-free survival (DFS) and overall survival (OS). Taken together, we provide novel evidence that miR-21 knockdown suppresses cell growth, migration and invasion partly by inhibiting PI3K/AKT activation via direct targeting PIK3R1 and reversing EMT in breast cancer. p85α downregulation defined a specific subgroup of breast cancer with shorter 5-year DFS and OS, which may require more aggressive treatment.

[Design of a Special Shaped Foam Dressing Based on Anatomy].

As the dressings currently used in clinic settings unflat shape in general, they can't be fitted completely on occiput, heel, elbow, knee and other body parts unflat. This paper developed one kind of foam dressing of special shape based on local anatomy. The foam dressing is waterproof and air permeable, it can cover the wound closely enough to prevent bacteria from invasion and infection. With a saturated absorption ratio of 1: 8 or higher, it can keep the wound clean and moisture by absorbing large amounts of wound inflammatory secretions and is almost completely permeable to oxygen and carbon dioxide. Assuring safety and effect meanwhile, it has better outcomes than common dressings in the same application settings.

[Detection of KRAS,NRAS and BRAF gene mutations in colorectal carcinoma].

OBJECTIVE: To investigate mutations frequencies of KRAS,NRAS and BRAF genes in colorectal carcinoma. METHODS: Tissue specimens from 200 colorectal cancer patients at diagnosis were collected and subject to KRAS,NRAS and BRAF mutation analyses by PCR-based direct DNA sequencing targeting exons 2, 3 and 4 of KRAS gene, exons 2, 3 and 4 of NRAS gene and exon 15 of BRAF gene. RESULTS: Activating mutations were detected in KRAS (44%, 88/200), NRAS (2%, 4/200) and BRAF (5%, 10/200) in this study cohort.Among KRAS mutations, 64.8% (57/88) occurred in codon 12 and 12.5% (11/88) occurred in codon 13. KRAS gene mutation in exon 3 mainly involved codons 59 and 61. KRAS gene mutation in exon 4 mainly involved codons 117 and 146. CONCLUSIONS: Mutations at exon 2 of KRAS gene have the highest frequency in colorectal carcinoma. Expanding the detection sites of KRAS gene combined with NRAS and BRAF genes may help to identify patients who will most likely benefit from targeted therapies.