Development and validation of a nomogram to predict cancer-specific survival of elderly patients with unresected gastric cancer who received chemotherapy.

This investigation aimed to explore the prognostic factors in elderly patients with unresected gastric cancer (GC) who have received chemotherapy and to develop a nomogram for predicting their cancer-specific survival (CSS). Elderly gastric cancer patients who have received chemotherapy but no surgery in the Surveillance, Epidemiology, and End Results Database between 2004 and 2015 were included in this study. Cox analyses were conducted to identify prognostic factors, leading to the formulation of a nomogram. The nomogram was validated using receiver operating characteristic (ROC) and calibration curves. The findings elucidated six prognostic factors encompassing grade, histology, M stage, radiotherapy, tumor size, and T stage, culminating in the development of a nomogram. The ROC curve indicated that the area under curve of the nomogram used to predict CSS for 3, 4, and 5 years in the training queue as 0.689, 0.708, and 0.731, and in the validation queue, as 0.666, 0.693, and 0.708. The calibration curve indicated a high degree of consistency between actual and predicted CSS for 3, 4, and 5 years. This nomogram created to predict the CSS of elderly patients with unresected GC who have received chemotherapy could significantly enhance treatment accuracy.

Can neoadjuvant chemoradiotherapy before lateral pelvic lymph node dissection improve local control and prognosis in rectal cancer patients with clinically suspected lateral lymph node metastasis? A multicenter lateral node study in China.

AIMS: Selective lateral pelvic lymph node (LPN) dissection (LPND) following neoadjuvant chemoradiotherapy (nCRT) for rectal cancer is widely recognized. This study aimed to determine the effects of nCRT before LPND on local control and prognosis of rectal cancer patients. MATERIALS AND METHODS: Data were retrieved from a prospective database for rectal cancer patients with clinical LPN metastasis receiving total mesorectal excision and LPND at three institutions between January 2012 and December 2019. Selection bias was minimized using propensity score matching (PSM) and short-term and clinical outcomes were compared. RESULTS: Patients (n = 213) were enrolled and grouped as either nCRT (n = 97) or non-nCRT (n = 116). PSM was used to identify 83 matched pairs. In the matched cohort, nCRT patients had a longer operation duration (310.6 vs. 265.0 min, P = 0.001), lower pathological LPN metastasis rate (32.5% vs. 48.2%, P = 0.040), and fewer harvested lymph nodes (22 vs. 25, P = 0.018) compared to the non-nCRT group. However, after PSM, the two groups had similar estimated overall 3-year survival (79.5% vs. 80.7%, P = 0.922), 3-year disease-free survival (66.1% vs. 65.5, P = 0.820), and 3-year local recurrence-free survival (88.6% vs. 89.7%, P = 0.927). Distant metastasis was the predominant recurrence pattern in the overall (45/58, 77.6%) and matched (33/44, 75.0%) cohorts. CONCLUSIONS: LPND without nCRT is effective and sufficient in preventing local recurrence in patients with LPN metastases. Future prospective randomized controlled studies are warranted to confirm these findings. Since systemic metastasis is the predominant recurrence pattern in patients with LPN metastasis post-LPND, improved perioperative systemic chemotherapy is needed to prevent micrometastasis.

Feasibility, Indications, and Prognostic Significance of Selective Lateral Pelvic Lymph Node Dissection After Preoperative Chemoradiotherapy in Middle/Low Rectal Cancer: Results of a Multicenter Lateral Node Study in China.

BACKGROUND: Lateral pelvic lymph node dissection after preoperative chemoradiotherapy can decrease local recurrence to lateral compartments, thereby providing survival benefits. OBJECTIVE: The safety of lateral pelvic lymph node dissection after preoperative chemoradiotherapy was investigated, and the surgical indications and survival benefits of lateral pelvic lymph node dissection were established on the basis of preoperative characteristics. DESIGN: A multicenter retrospective study. SETTINGS: Three hospitals in China. PATIENTS: Four hundred nine patients with clinical evidence of lateral pelvic lymph node metastasis. INTERVENTIONS: Patients who received lateral pelvic lymph node dissection were divided into 2 groups depending on whether they received chemoradiotherapy (n = 139) or not (n = 270). MAIN OUTCOME MEASURES: The safety, indications, and survival benefits of lateral pelvic lymph node dissection after preoperative chemoradiotherapy were investigated. RESULTS: The surgery times were significantly prolonged by preoperative chemoradiotherapy (291.3 vs 265.5 min; p = 0.021). Multivariate analysis demonstrated that poor/mucinous/signet-ring adenocarcinoma (OR = 4.42, 95% CI, 2.24-11.27; p = 0.031) and postchemoradiotherapy lateral pelvic lymph node short-axis diameter ≥7 mm (OR = 15.2, 95% CI, 5.89-53.01; p < 0.001) were independent predictive factors for lateral pelvic lymph node metastasis. Multivariate prognostic analysis showed that swollen lateral pelvic lymph nodes beyond the obturator or internal iliac as well as the involvement of 3 or more lateral pelvic lymph nodes were independent adverse prognostic factors. LIMITATIONS: The retrospective nature of the study and the small sample size were the limitations of this study. CONCLUSIONS: Preoperative chemoradiotherapy combined with lateral pelvic lymph node dissection is a practicable procedure with acceptable morbidity. Postchemoradiotherapy lateral pelvic lymph node short-axis diameter ≥7 mm and poor/signet/mucinous adenocarcinoma could be used for predicting lateral pelvic lymph node metastasis after chemoradiotherapy. However, lateral pelvic lymph node dissection should be carefully considered in patients with swollen lateral pelvic lymph nodes beyond the obturator or internal iliac region or involvement of multiple lateral pelvic lymph nodes. See Video Abstract at http://links.lww.com/DCR/C133 . VIABILIDAD, INDICACIONES E IMPORTANCIA PRONSTICA DE LA DISECCIN SELECTIVA DE GANGLIOS LINFTICOS PLVICOS LATERALES DESPUS DE QUIMIORRADIOTERAPIA PREOPERATORIA EN CNCER DE RECTO MEDIO/INFERIOR RESULTADOS DE UN ESTUDIO MULTICNTRICO DE GANGLIOS LATERALES EN CHINA: ANTECEDENTES:La disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria puede disminuir la recurrencia local en los compartimentos laterales, lo que brinda beneficios de supervivencia.OBJETIVO:Se investigó la seguridad de la disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria, y se establecieron las indicaciones quirúrgicas y los beneficios de supervivencia de la disección de los ganglios linfáticos pélvicos laterales en función de las características preoperatorias.DISEÑO:Estudio retrospectivo multicéntrico.ESCENARIO:Tres hospitales en China.PACIENTES:Cuatrocientos nueve pacientes con evidencia clínica de metástasis en los ganglios linfáticos pélvicos laterales.INTERVENCIONES:Los pacientes que recibieron disección de ganglios linfáticos pélvicos laterales se dividieron en dos grupos dependiendo de si recibieron quimiorradioterapia (n = 139) o no (n = 270).PRINCIPALES MEDIDAS DE RESULTADO:Se investigaron la seguridad, las indicaciones y los beneficios de supervivencia de la disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria.RESULTADOS:Los tiempos de cirugía se prolongaron significativamente con la quimiorradioterapia preoperatoria (291,3 vs 265,5 min, p = 0,021). El análisis multivariable demostró que el adenocarcinoma mal diferenciado/mucinoso/en anillo de sello (odds ratio = 4,42, intervalo de confianza del 95%, 2,24-11,27; p = 0,031) y el diámetro del eje corto de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia ≥7 mm (odds ratio = 15,2, intervalo de confianza del 95%, 5,89-53,01; p < 0,001) fueron factores predictivos independientes de metástasis en los ganglios linfáticos pélvicos laterales. El análisis pronóstico multivariable mostró que la inflamación de los ganglios linfáticos pélvicos laterales más allá del obturador o la ilíaca interna, así como la afectación de tres o más ganglios linfáticos pélvicos laterales, eran factores pronósticos adversos independientes.LIMITACIONES:La naturaleza retrospectiva del estudio y el pequeño tamaño de la muestra.CONCLUSIONES:La quimiorradioterapia preoperatoria combinada con la disección de los ganglios linfáticos pélvicos laterales es un procedimiento practicable con una morbilidad aceptable. Posterior a la quimiorradioterapia, el diámetro del eje corto de los ganglios linfáticos pélvicos laterales ≥7 mm y el adenocarcinoma pobre/en sello/mucinoso podrían usarse para predecir la metástasis en los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia. Sin embargo, la disección de los ganglios linfáticos pélvicos laterales debe considerarse cuidadosamente en pacientes con ganglios linfáticos pélvicos laterales inflamados más allá del obturador o de la región ilíaca interna o compromiso de múltiples ganglios linfáticos pélvicos laterales. Consulte Video Resumen en http://links.lww.com/DCR/C133 . (Traducción-Dr. Felipe Bellolio ).

Nomogram for predicting occurrence and prognosis of liver metastasis in elderly colorectal cancer patients: a population-based study.

Introduction: This study aimed to explore independent risk and prognostic factors in elderly patients with colorectal cancer liver metastasis (ECRLM) and generate nomograms for predicting the occurrence and overall survival (OS) rates of such patients. Method: Elderly colorectal cancer patients (ECRC) from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. External validation relied on Chinese patients from the China-Japan Union Hospital of Jilin University. Univariate and multivariate logistic regression analyses were employed to identify liver metastasis (LM) risk variables, which were used to create a nomogram to estimate LM probabilities in patients with ECRC. Univariate and multivariable Cox analyses were performed to identify prognostic variables and further derive nomograms that could predict the OS of patients with ERCLM. Differences in lifespan were assessed using the Kaplan-Meier analysis. Finally, the quality of the nomograms was verified using decision curve analysis (DCA), calibration curves, and receiver operating characteristic curves (ROC). Result: In the SEER cohort, 32,330 patients were selected, of those, 3,012 (9.32%) were diagnosed with LM. A total of 188 ECRLM cases from a Chinese medical center were assigned for external validation. LM occurrence can be affected by 13 factors, including age at diagnosis, marital status, race, bone metastases, lung metastases, CEA level, tumor size, Grade, histology, primary site, T stage, N stage and sex. Furthermore, in ECRLM patients, 10 variables, including age at diagnosis, CEA level, tumor size, lung metastasis, bone metastasis, chemotherapy, surgery, N stage, grade, and race, have been shown to be independent prognostic predictors. The results from both internal and external validation revealed a high level of accuracy in predicting outcomes, as well as significant clinical utility, for the two nomograms. Conclusion: We created two nomograms to predict the occurrence and prognosis of LM in patients with ECRC, which would contribute significantly to the improvement in disease detection accuracy and the formulation of personalized cures for that particular demographic.

A predictive model for early death in elderly colorectal cancer patients: a population-based study.

Purpose: The purpose of this study is to determine what variables contribute to the early death of elderly colorectal cancer patients (ECRC) and to generate predictive nomograms for this population. Methods: This retrospective cohort analysis included elderly individuals (≥75 years old) diagnosed with colorectal cancer (CRC) from 2010-2015 in the Surveillance, Epidemiology, and End Result databases (SEER) databases. The external validation was conducted using a sample of the Chinese population obtained from the China-Japan Union Hospital of Jilin University. Logistic regression analyses were used to ascertain variables associated with early death and to develop nomograms. The nomograms were internally and externally validated with the help of the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). Results: The SEER cohort consisted of 28,111 individuals, while the Chinese cohort contained 315 cases. Logistic regression analyses shown that race, marital status, tumor size, Grade, T stage, N stage, M stage, brain metastasis, liver metastasis, bone metastasis, surgery, chemotherapy, and radiotherapy were independent prognostic factors for all-cause and cancer-specific early death in ECRC patients; The variable of sex was only related to an increased risk of all-cause early death, whereas the factor of insurance status was solely associated with an increased risk of cancer-specific early death. Subsequently, two nomograms were devised to estimate the likelihood of all-cause and cancer-specific early death among individuals with ECRC. The nomograms exhibited robust predictive accuracy for predicting early death of ECRC patients, as evidenced by both internal and external validation. Conclusion: We developed two easy-to-use nomograms to predicting the likelihood of early death in ECRC patients, which would contribute significantly to the improvement of clinical decision-making and the formulation of personalized treatment approaches for this particular population.

The feasibility and technical strategy of a fascia space priority approach in laparoscopic lateral lymph node dissection for advanced middle and low rectal cancer: a retrospective multicentre study.

INTRODUCTION: Laparoscopic lateral lymph node dissection (LLND) is an important treatment for patients with lateral lymph node metastasis. AIM: To assess the technical feasibility and investigate the surgical outcomes after LLND using the fascia space priority approach for patients with advanced middle and low rectal cancer. MATERIAL AND METHODS: Consecutive patients undergoing laparoscopic LLND using the fascia space priority approach from June 2017 to June 2020 were identified from 12 medical centres in mainland China. Three anatomic fascia spaces were dissected to establish the boundaries of the LLND, and the obturator and internal iliac lymph nodes were excised in an en bloc manner. Retrospective clinical data including patient characteristics, surgical details, and pathology were analysed. RESULTS: A total of 112 patients were identified. All surgeries were completed laparoscopically with no conversions. The mean operation time was 343.6 ±103.8 min for the entire procedure. The median blood loss was 100 ml (range: 100-700 ml). The median lymph node yield was 6 (range: 1-41), and lymph nodes were positive in 39.3% (44/112) of the patients. Sixteen (14.3%) patients had Clavien-Dindo I-II complications, no Clavien-Dindo III-IV complications were identified. The incidence of complications between the bilateral dissection group and the unilateral dissection group was not statistically different (p = 0.19). The complication rate between the "nCRT" group and the "no nCRT" group was not significantly different (p = 0.62) either. There were no perioperative deaths. CONCLUSIONS: Laparoscopic LLND using the fascia space priority approach is feasible and safe for patients with lateral lymph node metastasis.

HER2 Overexpression and Mismatch Repair Deficiency are Correlated with Malignancy in Colorectal Cancer.

PURPOSE: This study was designed to investigate the correlation between the expression of human epidermal growth factor receptor 2 (HER2), mismatch repair (MMR), and clinicopathological parameters and serum tumor markers in a total of 522 resection samples materials from colorectal cancer (CRC) patients. These data were also used to determine the links between HER2 and MMR expression and prognosis. METHODS: We conducted a retrospective analysis of the clinical data from 522 CRC patients. Immunohistochemistry (IHC) was used to detect HER2 overexpression and MMR deficiency (dMMR) in tumor specimens which were then correlated with various clinicopathological parameters. Prognostic value for HER2 and MMR expression was then evaluated using the data from 105 CRC patients. RESULTS: HER2 overexpression was identified in 35.63% of the samples evaluated in this study, while the total dMMR rate was 12.64%. Expression of HER2 and several, MMR proteins (MLH1, MSH-2, MSH-6, and PMS-2) were then correlated with tumor location. HER2 overexpression is significantly associated with increased depth of tumor invasion, lymph node metastasis, distant metastases, pTNM staging, vascular invasion, nerve infiltration, and serum carcinoembryonic antigen (CEA) levels. HER2 overexpression and dMMR increased with advancing clinical stage. In addition, deficiencies in MLH1 and PMS2 correlated with HER2 overexpression. Finally, the prognostic evaluations revealed that HER2 overexpression was closely associated with poorer clinical outcomes. CONCLUSION: HER2 overexpression is significantly correlated with multiple clinicopathological parameters resulting in a poorer prognosis. Moreover, the prognosis of patients with HER2 overexpression was worse, confirming its significance during disease assessment. In clinical practice, clinicians should pay close attention to the HER2 profile of patients as they may require more extensive clinical intervention. In addition, deficiencies in MLH1, MSH-2, MSH-6, or PMS-2 correlate with tumor location, and MLH1 and PMS2 expression is associated with lymph node metastasis and pTNM stage, suggesting that these may be additional markers in CRC risk assessments.

Short-term outcomes of medium-low rectal cancer treated by taTME and experience of 22 cases.

BACKGROUND AND METHODS: Transanal total mesorectal excision (taTME) is a novel radical resection technique that may address the unsatisfactory functional and oncological outcomes of medium-low rectal cancers. Although its oncological safety remains unclear, taTME has demonstrable value in surgery, complications, and oncological outcomes. Here, we explore the short-term outcomes of rectal cancer after taTME and discuss the surgical experience. Twenty-two patients with medium-low rectal cancer who underwent taTME were retrospectively evaluated. Comprehensive demographic, oncological, and clinical data were analyzed and the perioperative state and postoperative follow-up were evaluated. RESULTS: Over a median follow-up period of 24.4 (4-36) months, local recurrence occurred in one patient at 6 months postsurgery. Fecal incontinence was the most common postoperative complication, and 3-6 months of pelvic-floor-rehabilitation training greatly improved  anal function CONCLUSIONS: taTME achieved satisfactory short-term outcomes in oncological complications and postoperative functions. Accurate intraoperative anatomical location, identification of the rectovesical fascia, and neuroprotection are critical. However, this procedure has a steep learning curve, and large samples and multicenter studies are required to substantiate its effectiveness. DISCUSSION: We retrospectively analyzed the oncological and functional prognosis of 22 patients with colorectal cancer undergoing taTME surgery and preliminarily concluded taTME can be regarded as a safe and feasible treatment.

Multicenter investigation of bowel evacuation function after transanal total mesorectal excision for mid-low rectal cancer.

PURPOSE: To determine the effect of transanal total mesorectal excision (taTME) procedure on the postoperative bowel evacuation function of patients with low rectal cancer. METHODS: Bowel evacuation function was investigated in 316 patients with rectal cancer after taTME in 18 hospitals in China. Low anterior resection syndrome (LARS) score, Wexner score, and EORTC QLQ-C30 were used for functional evaluation. The association between perioperative risk factors and LARS score was determined by univariate and multivariate analyses. RESULTS: The prevalence rate of no LARS, minor LARS, and major LARS in patients after taTME was 39.9%, 28.2%, and 31.9%, respectively. The two most frequently reported symptoms of LARS after taTME were bowel clustering (72.8%) and fecal urgency (63.3%). Patients with major LARS had significantly higher Wexner score and worse global health status and financial difficulties according to the EORTC QLQ-C30 questionnaire than those without major LARS. Preoperative chemoradiotherapy was an independent risk factor of major LARS occurrence after taTME (OR: 3.503, P = 0.044); existing preoperative constipation (OR: 0.082, P = 0.040) and manual anastomosis (OR: 4.536, P = 0.021) were favorable factors affecting bowel evacuatory function within 12 months after taTME, but for patients whose follow-up time was longer than 12 months, postoperative chemoradiotherapy (OR: 8.790, P = 0.001) and defunctioning stoma (OR: 3.962, P = 0.010) were independent risk factors. CONCLUSIONS: The bowel evacuation function after taTME is acceptable. Perioperative chemoradiotherapy, anastomotic method, and preoperative constipation are factors associated with bowel dysfunction after taTME.

Clinical significance and diagnostic value of serum NSE, CEA, CA19-9, CA125 and CA242 levels in colorectal cancer.

The present study investigated the value of combinations of five specific tumor biomarkers for the diagnosis of colorectal cancer (CRC): Neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cancer antigen (CA)19-9, CA125 and CA242. Associations between these markers and clinicopathological characteristics (including the Tumor-Node-Metastasis stage) were also assessed. Serum levels of the 5 markers were compared between 358 patients with CRC and 298 healthy individuals (CRC and control group, respectively). The NSE concentration of the CRC group was significantly higher compared with the control. Furthermore, patients at clinical stage III+IV exhibited significantly higher NSE levels compared with those at stage I+II. The serum NSE level of N+ patients was significantly higher compared with the N- group, and the NSE level of M1 patients was significantly compared with the M0 group. NSE level was also significantly associated with tumor stage, lymph node metastasis, distant metastasis and hematochezia. The area under the receiver operating characteristic curve (AUC) for NSE in CRC was 0.766, which was significantly higher than that of the other four markers, which ranged from 0.560-0.682. The AUC of NSE, CEA, CA19-9, CA125, CA242 combined was significantly higher compared with any of the markers individually (range, 0.796-0.858). Therefore, serum NSE may be a good clinical tool for the auxiliary diagnosis of colorectal cancer. Besides, the combination of NSE, CEA, CA19-9, CA125 and CA242 was significantly more sensitive compared with NSE alone. Thus, the combined detection of the 5 tumor markers may be more useful for the diagnosis of CRC.

Correlation study between serum neuro-specific enolase and gastric and colorectal cancers.

This study investigated the diagnostic value of preoperative serum neuro-specific enolase (NSE) in gastric cancer (GC) and colorectal cancer (CRC), and the diagnostic viability of combined serum NSE, carcinoembryonic antigen (CEA), cancer antigen (CA)19-9, and CA242.Patients with GC and CRC, and a healthy control group (n = 666 and 266, respectively) were compared with regard to NSE, CEA, CA19-9, and CA242 serum levels. NSE was analyzed for associations with clinicopathological parameters. To estimate the diagnostic potential of NSE, a receiver operating characteristic curve was constructed and the area under the curve (AUCs) was calculated for different patient subgroups.The median serum NSE level of the tumor group (20.925 ng/mL) was significantly higher than that of the control (15.190 ng/mL). Serum NSE was associated with pathological tumor-node-metastasis staging, lymph node metastasis, distant metastasis, vascular invasion, and nerve infiltration. The area under the receiver operating characteristic curve (AUC) for NSE in GC and CRC (0.769) was higher than for the other 3 markers (0.571-0.680). The AUC of the combined markers was higher than for any of the markers individually (0.778-0.810).The AUC for NSE alone suggests it may be an independent tumor marker, and useful for diagnosis of GC and CRC. However, the AUC for combined NSE, CEA, CA19-9, and CA242 was higher and thus potentially more diagnostic value.

Clinical significance of serum neuron-specific enolase in gastric adenocarcinoma.

As a biomarker, neuron-specific enolase (NSE) has been widely recognized in the diagnosis of benign diseases and malignant tumors. This study aimed to investigate the potential diagnostic value of NSE in patients with gastric adenocarcinoma.Serum levels of the NSE were compared between 219 patients with gastric adenocarcinoma and 298 healthy individuals, NSE and clinicopathological parameters were analyzed. Meanwhile, to evaluate the diagnostic capability of NSE, the receiver operating characteristic (ROC), and area under curve (AUC) was calculated.In the present study, the median serum NSE level of the patient group was 20.770 ng/mL, which was higher than that of the control group 15.625 ng/mL (P < .05). Serum NSE level in patients group compared with healthy control was statistically significant (P < .05). Serum NSE level was associated with pathological tumor-node-metastasis (pTNM) staging, lymph node metastasis, and distant metastasis in patients with gastric adenocarcinoma. Besides, the AUC of NSE in gastric adenocarcinoma was 0.742, which was higher than those of the other 3 markers (0.573-0.644). Besides, the AUC of the combined 4 markers was higher than any individual marker (0.778).Serum NSE detecting may have good value for diagnosis of gastric adenocarcinoma. Besides, the combination of NSE, CEA, CA19-9, and CA242 performed even better than any single marker. Thus, the combined detection of the 4 tumor markers may be more useful for the diagnosis of gastric adenocarcinoma.

Perianal Paget disease treated with wide excision and thigh skin flap reconstruction: a case report and review of literature.

RATIONALE: Extramammary Peget disease (EMPD) is a rare tumor, which typically occurs in the perianal regions. Perianal Paget disease (PPD) was first reported in 1893, and which has only 180 cases that have been reported in literature. The rarity of the disease means that no large studies have been made, and so the optimal treatment for this disease still remains controversial. PATIENT CONCERNS: In this case, we reported a 65-years-old female patient with PPD. The patient suffered intermittent pruritus in the perianal region for 1 year. She had neither genitourinary nor gastrointestinal symptoms. Local examination revealed a whitish gray skin lesion in the left perianal area with a 3 × 3 cm size. DIAGNOSES: The perianal skin biopsy was consistent with EMPD. Then the patient underwent a screening colonoscopy, gynecological ultrasonography, and whole-body computed tomography to exclude underlying malignancy. INTERVENTIONS: The patient underwent wide local excision with margin control by frozen section examination and posterior thigh flap reconstruction. Subsequently follow-up remains 6 years. OUTCOMES: The operation was successful. The total operation time was 296 minutes, and the estimated blood loss was 120 mL. The patient recovered without any complication and discharged home on the sixth postoperative day. After 6 years' follow-up, there was no evidence of recurrence and no influence in the anal bowel control function. LESSONS: PPD is a rare disorder; the current knowledge on diagnose and treatment is based on small case series. Thus, it is complicated to elaborate a consensus on diagnostic and treatment guidelines. Wide local excision remains the treatment of choice with a variety of adjuvant therapies. Our method has an advantage which is the posterior thigh flap could be designed in accordance with the defect of the perianal. It is mandatory that the patient must accept a long-term follow-up to detect local recurrence and to distant carcinoma.

Double laparoscopy assisted cylindrical abdominal-perineal resection for low rectal cancer with 4 cases report.

INTRODUCTION: Rectal cancer is a common cancer worldwide. Low rectal cancer exhibits a tendency for recurrence. Surgical resection is an important treatment for rectal cancer. Cylindrical abdominal-perineal resection is suitable for patients with low rectal cancer and has helped improve the prognosis of these patients. However, there are some difficulties during the operation. Especially the perineal area operation cannot be performed under direct vision, which affects the quality of surgical resection. To resolve these constraints, our group designed double laparoscopy assisted cylindrical abdominal-perineal resection for low rectal cancer. CONCLUSION: The procedure effectively solved these problems and reduced the operation time with no increase in surgery complications.

MiR-144-3p inhibits cell proliferation and induces apoptosis in multiple myeloma by targeting c-Met.

MicroRNA-144-3p (miR-144-3p) has been implicated in the development of many types of cancer. However, its role in multiple myeloma (MM) remains largely unknown. In this study, we found that miR-144-3p was downregulated in both MM cell lines and plasma from patients with MM. In vitro studies further showed that transfection of an miR-144-3p mimic into MM cells inhibited their proliferation and colony formation, and promoted cell cycle arrest at the G0/G1 phase and apoptosis. In addition, we found that miR-144-3p could directly target the 3'-untranslated region of cellular-mesenchymal to epithelial transition factor (c-MET) and suppress c-MET expression and its downstream signaling pathway (PI3K/AKT). Rescue experiments revealed that overexpression of c-MET partially reversed the inhibition effect of miR-144-3p in MM cells. In vivo studies confirmed that restoration of miR-144-3p suppressed tumor growth in xenograft nude mice by repressing c-MET. Overall, these findings demonstrate that miR-144-3p functions as a tumor suppressor in MM by targeting c-MET, suggesting that miR-144-3p might serve as a potential therapeutic target in MM.

Identification of key genes in colorectal cancer using random walk with restart.

As the most common type of cancer and the second leading cause of cancer-associated mortality, colorectal cancer (CRC) has received increasing attention. The aim of the present study was to investigate the mechanisms of CRC by analyzing the microarray dataset, GSE32323. The GSE32323 dataset was downloaded from the Gene Expression Omnibus, and included 17 pairs of matched cancer and normal colorectal tissue samples. The differentially expressed genes (DEGs) were screened using the Linear Models for Microarray Data package and a search of CRC genes, also denoted as seed genes, was performed using the Online Mendelian Inheritance in Man database. Subsequently, the protein­protein interaction (PPI) network was downloaded from the Search Tool for the Retrieval of Interacting Genes database and the sub­network (CRC.PPI) of the DEGs and seed genes were obtained. In addition, the top 50 nodes with highest affinity scores in the CRC.PPI were identified using random walk with restart analysis. The potential functions of the DEGs included in the top 50 nodes were analyzed using the Database for Annotation, Visualization and Integrated Discovery online tool. Using the Drug Gene Interaction database, drug­gene interaction analysis was performed to identify antineoplastic drug interacts with genes. A total of 1,640 DEGs between the CRC and normal samples were screened. The obtained seed genes included cyclin D1 (CCND1) and aurora kinase A (AURKA). The enriched functions for the 31 DEGs in the PPI network of the top 50 nodes were predominantly associated with cell cycle. The DEGs may function in CRC by interacting with other genes in the PPI network of the top 50 nodes, for example, DEP domain­containing MTOR­interacting protein (DEPTOR)­CCND1, AURKA­breast carcinoma amplified sequence­1 (BCAS1), CCND1­BCAS1, CCND1­neural precursor cell expressed developmentally downregulated 9 (NEDD9) and CCND1­mitogen­activated protein kinase kinase 2 (MAP2K2). Only three DEGs (CCND1, AURKA and DEPTOR) had interactions with their corresponding antineoplastic drugs. Taken together, DEPTOR, AURKA, CCND1, BCAS1, NEDD9 and MAP2K2 may act in CRC.

miR-152 functions as a tumor suppressor in colorectal cancer by targeting PIK3R3.

Accumulating evidence showed that microRNA-152 (miR-152) was frequently downregulated, and functioned as tumor suppressor in many cancers, but little is known about its biological role and intrinsic regulatory mechanisms in colorectal cancer (CRC). Here, we explored the potential role of miR-152 in CRC and the possible molecular mechanisms. Our results proved that miR-152 expression was downregulated in CRC cell lines and tissue samples, and its expression was inversely correlated with advanced tumor-node-metastasis (TNM) stage (P < 0.01) and lymph node metastasis (P < 0.01). Function assays demonstrated that restoring the expression of miR-152 in CRC cells dramatically reduced the cell proliferation and cell migration and invasion and promoted apoptosis and caspase-3 activity in vitro, as well as suppressed tumor growth in vivo. Mechanistic investigations defined phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) as a direct and functional downstream target of miR-152. In addition, we also found that PIK3R3 expression was upregulated and was inversely correlated with miR-152 expression in clinical CRC tissues. Downregulation of PIK3R3 mimicked the tumor-suppressive effects of miR-152 overexpression in CRC cells. Taken together, these results elucidated the function of miR-152 in CRC progression and suggested that miR-152 might function as tumor suppressor in CRC by targeting PIK3R3.

MicroRNA-613 targets FMNL2 and suppresses progression of colorectal cancer.

Increasing evidence indicates that dysregulation of miRNAs is involved in the initiation and progression of colorectal cancer (CRC). MicroRNA (miR)-613 has been reported to function as a tumor suppressor in many cancers. However, the precise role of miR-613 in CRC progression is unclear. This study aimed to investigate the role and underlying mechanism of miR-613 in growth and metastasis of CRC. Real-time quantitative PCR (qPCR) and western blot techniques were used to assess expression of miR-613 and formin-like 2 (FMNL2) in CRC cell lines and tissues. Luciferase reporter assays were conducted to investigate the association between miR-613 and FMNL2. Proliferation, wound healing, and transwell invasion assays, as well as flow cytometric analysis, were performed to evaluate the effect of miR-613 on proliferation, migration, invasion, and cell-cycle status, respectively, of CRC cells. We found that miR-613 was significantly downregulated in CRC cell lines and tissue samples, and correlated closely with TNM stage. miR-613 suppressed CRC cell proliferation, migration, and invasion, and induced cell-cycle arrest at G1 phase. FMNL2 was identified as a direct target of miR-613 in CRC cells. Importantly, FMNL2 overexpression rescued miR-613-induced suppression of proliferation, migration, and invasion of CRC cells. These results suggest that miR-613 functions as a tumor suppressor in the progression of CRC by regulating FMNL2.

Prognostic role of SIRT1 in hepatocellular carcinoma.

OBJECTIVE: To determine the clinical significance of silent mating type information regulation 2 homolog 1 (SIRT1) expression in Hepatocellular Carcinoma (HCC) and its association with P53 and Yes-associated protein 2 (YAP2) expression. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun, China, from January 2000 to January 2010. METHODOLOGY: Tissue microarray technique and immunohistochemistry were conducted to detect the expression of SIRT1, P53 and YAP2 proteins in 300 self-paired HCC samples. Associations with clinicopathologic manifestations were analyzed, overall survival analysis and multivariate analysis were performed. RESULTS: By tissue microarray technique and immunohistochemistry on 300 self-paired HCC samples, it was found that SIRT1, P53 and YAP2 were significantly overexpressed in HCC tumor tissues compared with adjacent non-tumor tissues. SIRT1 immunostaining localized both in the nucleus (145/300, 48.3%) and the cytoplasm (70/300, 23.3%), and the overexpression of nuclear SIRT1 was positively related to the overexpression of P53 and YAP2. Survival analysis showed that nuclear SIRT1, P53 and YAP2 overexpression predicted poor overall survival while cytoplasmic SIRT1 overexpression predicted longer overall survival. Multivariate analysis showed nuclear SIRT1 and P53 overexpression as independent tumor promoters while cytoplasmic SIRT1 overexpression as an independent tumor suppressor. CONCLUSION: SIRT1 was overexpressed in HCC and the expression was positively related to P53 and YAP2 expression. As the nuclear SIRT1 functions as a tumor promoter and cytoplasmic SIRT1 functions as a tumor suppressor, the role of SIRT1 in HCC should be reconsidered.

A synergistic combination therapy with paclitaxel and doxorubicin loaded micellar nanoparticles.

Doxorubicin was chemically conjugated to a biodegradable polymeric carrier as a polymer-doxorubicin (polymer-Dox) conjugate via an acid labile Schiff-base bond. Then, paclitaxel was physically encapsulated by the polymer-Dox conjugate to self assemble in water as micellar nanoparticles with both doxorubicin and paclitaxel in one nanoparticle. In this way, doxorubicin and paclitaxel were combined. The preparation of the polymer-doxorubicin conjugates, encapsulation of paclitaxel, characterization of nanoparticles was systematically studied and the biological evaluation of the free drug combination as well as the micellar platform combination in vitro was thoroughly detailed.