Assessing Severity of Low Anterior Resection Syndrome After Intersphincteric Resection for Ultralow Rectal Cancer: A Pilot Study Using an Exploratory Instrument.

BACKGROUND: The Delphi consensus identified 8 symptoms and 8 consequences as the highest priorities for defining low anterior resection syndrome. OBJECTIVE: To describe an exploratory scoring instrument correlating the Delphi consensus on low anterior resection syndrome with functional and quality-of-life scores following intersphincteric resection for ultralow rectal cancer. DESIGN: This was a prospective pilot study. In accordance with the Wexner incontinence score, 5 frequency responses ranging from never (score 0) to always (score 4) were used to measure the severity of symptom- and consequence-specific variables. SETTINGS: Colorectal surgery referral center. PATIENTS: Among 161 eligible patients, 137 participants (85%) completed an electronic self-assessment survey regarding function and quality of life at scheduled follow-up, including 3 to 6, 12, and ≥24 months after ileostomy reversal. MAIN OUTCOME MEASURES: Outcome measures included patient-reported severity of the identified priorities, and their correlation with condition-specific quality of life. RESULTS: The most frequent symptom and consequence were "emptying difficulties" and "dissatisfaction with the bowels," respectively. Aside from "emptying difficulties," the proportions of negative symptom domains increased after reversal. In particular, neither the frequency responses nor the severity scores of "emptying difficulties" differed between groups. The percentages of "always" selection for consequence domains improved at 12-month follow-up, whereas a higher rate was observed at 24 months, except for "toilet dependence" and "dissatisfaction with the bowels." We found significant improvements in the summary score of the Fecal Incontinence Quality-of-Life Scale ( p = 0.04) and our exploratory instrument ( p = 0.009) but not in functional scores measured by traditional questionnaires. Furthermore, the condition-specific quality of life strongly correlated with the Delphi consensus severity score ( rs = -0.73). LIMITATIONS: Single-institution data and limited sample size. CONCLUSIONS: The important priorities identified by the Delphi consensus might enable a comprehensive overview and a better assessment of low anterior resection syndrome after intersphincteric resection. See Video Abstract . EVALE LA GRAVEDAD DEL SNDROME DE RESECCIN ANTERIOR BAJA DESPUS DE LA RESECCIN INTERESFINTRICA PARA EL CNCER DE RECTO ULTRABAJO UN ESTUDIO PILOTO QUE UTILIZA UN INSTRUMENTO EXPLORATORIO: ANTECEDENTES:El consenso Delphi identificó ocho síntomas y ocho consecuencias como las máximas prioridades para definir el síndrome de resección anterior baja.OBJETIVO:Describir un instrumento de puntuación exploratorio que correlaciona el consenso Delphi sobre el síndrome de resección anterior baja con puntuaciones funcionales y de calidad de vida después de la resección interesfinteriana para el cáncer de recto ultrabajo.DISEÑO:Este fue un estudio piloto prospectivo. De acuerdo con la puntuación de incontinencia de Wexner, se utilizaron cinco respuestas de frecuencia que van desde nunca (puntuación 0) hasta siempre (puntuación 4) para medir la gravedad de las variables específicas de los síntomas y las consecuencias.AJUSTES:Centro de referencia de cirugía colorrectal.PACIENTES:Entre 161 pacientes elegibles, 137 (85%) participantes completaron una encuesta electrónica de autoevaluación sobre la función y la calidad de vida en el seguimiento programado, incluidos 3 a 6, 12 y ≥ 24 meses después de la reversión de la ileostomía.MEDIDAS PRINCIPALES DE RESULTADO:Las medidas de resultado incluyeron la gravedad de estas prioridades informada por los pacientes, así como su correlación con la calidad de vida específica de la afección.RESULTADOS:El síntoma y la consecuencia más frecuentes fueron "dificultades para vaciar" e "insatisfacción con las deposiciones", respectivamente. Aparte de las "dificultades de vaciado", las proporciones de dominios de síntomas negativos aumentaron después de la reversión. En particular, tanto las respuestas de frecuencia como las puntuaciones de gravedad de las "dificultades para vaciar" no difirieron entre los grupos. Los porcentajes de "opción siempre" para los dominios de consecuencias mejoraron a los 12 meses de seguimiento, mientras que se observó una tasa más alta a los 24 meses después, excepto para "dependencia del baño" e "insatisfacción con los intestinos". Encontramos mejoras significativas en la puntuación resumida de la Escala de calidad de vida de incontinencia fecal ( p = 0,04) y nuestro instrumento exploratorio ( p = 0,009), pero no en las puntuaciones funcionales medidas con los cuestionarios tradicionales. Además, la calidad de vida específica de la condición se correlacionó fuertemente con la puntuación de gravedad del consenso Delphi (rs = -0,73).LIMITACIONES:Datos de una sola institución y tamaño de muestra limitado.CONCLUSIONES:Las importantes prioridades identificadas por el consenso Delphi podrían permitir una visión global y una mejor evaluación del síndrome de resección anterior baja después de la resección interesfintérica. (Traducción-Dr. Yesenia Rojas-Khalil ).

Assessing the influence of parameters on tissue welding in small bowel end-to-end anastomosis in vitro and in vivo.

BACKGROUND: The use of high-frequency electric welding technology for intestinal end-to-end anastomosis holds significant promise. Past studies have focused on in vitro, and the safety and efficacy of this technology is uncertain, severely limiting the clinical application of this technology. This study investigates the impact of compression pressure, energy dosage, and duration on anastomotic quality using a homemade anastomosis device in both in vitro and in vivo settings. METHODS: Two hundred eighty intestines and 5 experimental pigs were used for in vitro and in vivo experiments, respectively. The in vitro experiments were conducted to study the effects of initial pressure (50-400 kpa), voltage (40-60 V), and time (10-20 s) on burst pressure, breaking strength, thermal damage, and histopathological microstructure of the anastomosis. Optimal parameters were then inlaid into a homemade anastomosis and used for in vivo experiments to study the postoperative porcine survival rate and the pathological structure of the tissues at the anastomosis and the characteristics of the collagen fibers. RESULTS: The anastomotic strength was highest when the compression pressure was 250 kPa, the voltage was 60 V, and the time was 15 s. The degree of thermal damage to the surrounding tissues was the lowest. The experimental pigs had no adverse reactions after the operation, and the survival rate was 100%. 30 days after the operation, the surgical site healed well, and the tissues at the anastomosis changed from immediate adhesions to permanent connections. CONCLUSION: High-frequency electric welding technology has a certain degree of safety and effectiveness. It has the potential to replace the stapler anastomosis in future and become the next generation of new anastomosis device.

Conformal sphincteric resection for ultra-low rectal cancer located below the dentate line: A pilot report.

AIM: Sphincter-sparing surgery can be achieved in most cases of low rectal cancer with the development of intersphincteric resection. However, abdominoperineal resection is still inevitable for patients with tumours located below the dentate line. To address this, we have developed a procedure called conformal sphincteric resection (CSR) in which the corresponding part of the subcutaneous portion of the external anal sphincter and the perianal skin on the tumour side is removed to achieve a safe distal resection margin and lateral resection margin while the dentate line and the internal anal sphincter on the tumour-free side are preserved as much as possible, to achieve sphincter preservation without compromising oncological safety and functional acceptability, and to render tumour location no longer a contraindication for sphincter-sparing surgery. This is the first study to describe the concept, indication and surgical procedure of CSR and to report its preliminary surgical, oncological and functional results. METHODS: This is a retrospective, single-centre, single-arm pilot study conducted at Huashan Hospital, Fudan University. Demographic, clinicopathological, oncological and functional follow-up data were collected from 20 consecutive patients with rectal tumours located below the dentate line who underwent laparoscopic CSR by the same surgical team from June 2018 to March 2022. RESULTS: The mean distance of the tumour's lower edge from the anal verge was 13.1 ± 6.0 mm. The mean distal resection margin was 10.6 ± 4.3 mm. All circumferential resection margins were negative. There were no instances of perioperative mortality. The complication rate was 25% but all were Clavien-Dindo Grade I. Among the 20 cases, 17 were diagnosed with adenocarcinoma, one with squamous cell carcinoma and two with adenoma featuring high-grade intraepithelial neoplasia. Pathological TNM staging revealed two, seven, five, five and one case(s) in Stages 0, I, II, III and IV, respectively. The median follow-up period was 20 months (interquartile range 22 months), with no withdrawals. The overall and disease-free survival rates were both 95%. The mean Wexner incontinence score and low anterior resection syndrome score recorded 18 months following diverting ileostomy closure were 6.3 ± 3.8 and 27.3 ± 3.6, respectively. CONCLUSIONS: This study has proposed the CSR procedure for the first time, which is a technically feasible, oncologically safe and functionally acceptable procedure for carefully selected patients with rectal tumours located below the dentate line.

Does anastomotic leakage after intersphincteric resection for ultralow rectal cancer influence long-term outcomes? A retrospective observational study.

PURPOSE: To determine whether anastomotic leakage (AL) following intersphincteric resection (ISR) for ultralow rectal cancer (uLRC) is associated with long-term negative outcomes. METHODS: Between June 2011 and January 2022, 236 consecutive patients who underwent ISR with diverting ileostomy for uLRC were included. The primary outcome was long-term clinical consequences of AL, including chronic stricture, stoma reversal, and oncological and functional results. RESULTS: Forty-one (17.4%) patients developed symptomatic AL, whereas only two (0.8%) required re-laparotomy due to severe leakage. Patients with leaks had a significantly increased incidence of chronic stricture (29.3% vs. 8.7%, P = 0.001) and stoma non-reversal (34.1% vs. 4.6%, P < 0.0001) than controls. The severe consequences were particularly common in patients with anastomotic separation, resulting in 60% of those presenting with chronic stricture and 50% ending up with stoma non-reversal. After a median follow-up of 59 (range, 7-139) months, AL did not compromise long-term oncological outcomes, including tumor recurrence (9.8% vs. 5.6%, P = 0.3), 5-year disease-free, and overall survival (73.4% vs. 74.8% and 85.1% vs. 85.4%, P = 0.56 and P = 0.55). A total of 149 patients with bowel continuity who completed self-assessment questionnaires were enrolled for functional evaluation. The median follow-up was 24 (range, 12-94) months after ileostomy reversal, and functional results were comparable between patients with and without leaks. CONCLUSION: AL is an unfortunate reality for patients who underwent ISR for uLRC, but the rate of severe leakage is limited. Leaks contribute to possible adverse impacts on chronic stricture and stoma non-reversal, especially for patients with anastomotic separation. However, long-term oncological and functional results may not be compromised. TRIAL REGISTRATION: Chictr.org.cn identifier: ChiCTR-ONC-15007506 and ChiCTR2100051614.

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.

Circulating exosomal CPNE3 as a diagnostic and prognostic biomarker for colorectal cancer.

Exosomal proteins are emerging as relevant diagnostic and prognostic biomarkers for cancer. This study was aimed at illustrating the clinical significance of exosomal Copine III (CPNE3) purified from the plasma of colorectal cancer (CRC) patients. The CPNE3 expression levels in CRC tissues were analyzed by real-time PCR, western blot, and immunohistochemistry. Plasma exosomes were isolated to examine the CPNE3 level using ELISA. Pearson's correlation analysis was performed to investigate the CPNE3 levels between CRC tissues and matched plasma samples. Receiver operating characteristic curve analysis was developed to measure the diagnostic performance of exosomal CPNE3. The Kaplan-Meier method and Cox's proportional hazards model were utilized to determine statistical differences in survival times. CPNE3 showed increased expressions in the CRC tissues. A moderately significant correlation was found between CPNE3 expression in CRC tissues by immunohistochemistry and matched serum exosomal CPNE3 expression by ELISA (r = 0.645,(r = 0.645, p < 0.001). < 0.001). Exosomal CPNE3 yielded a sensitivity of 67.5% and a specificity of 84.4% in CRC at the cutoff value of 0.143 pg per 1ug1 ug exosome. Combined data from carcinoembryonic antigen and exosomal CPNE3 achieved 84.8% sensitivity and 81.2% specificity as a diagnostic tool. CRC patients with lower exosomal CPNE3 levels had substantially better disease-free survival (hazard ratio [HR], 2.9; 95% confidence interval [CI]: 1.3-6.4; p = 0.009) = 0.009) and overall survival (HR, 3.4; 95% CI: 1.2-9.9; p = 0.026) = 0.026) compared with those with higher exosomal CPNE3 levels. Exosomal CPNE3 show potential implications in CRC diagnosis and prognosis.

Colorectal cancer exosomes induce lymphatic network remodeling in lymph nodes.

The lymphatic network remodeling may guide tumor metastasis in a sentinel lymph node (SLN). Although tumor-derived exosomes have been demonstrated to modify the microenvironment in adjacent organs and initiate a premetastatic niche, their influence on the lymphatic network in SLNs has not been explained. Here, we show that CT26 cell exosomes (Exo) promote the proliferation of lymphatic endothelial cells and the formation of lymphatic network in SLN, facilitating the SLN metastasis of colorectal cancer (CRC). Uptake of Exo by macrophages promoted VEGFC secretion both in vivo and in vitro. Exo increased the frequency of F4/80+ macrophages in the SLN. Macrophage ablation by clodrosome prevented the exosomal effect on lymphatic network remodeling and SLN metastasis. Exosomal IRF-2 was highly expressed in serum exosomes isolated from CRC patients with LN metastasis relative to patients without LN metastasis and healthy controls. Mechanistically, exosomal IRF-2 induced the release of VEGFC by macrophages. An IRF-2 knockdown attenuated the lymphatic network remodeling in the SLN and suppressed the SLN metastasis. Our data suggest that exosomal IRF-2 remodels the lymphatic network in an SLN and may predict the development of CRC LN metastases.

Prognostic impact of circulating tumor cells in patients with ampullary cancer.

Circulating tumor cells (CTCs) are an important topic of investigation for both basic and clinical cancer research. In this prospective study, we evaluated the clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62 consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy controls for their CTC content. Combined data from immunostaining of CD45, 4',6-diamidino-2-phenylindole (DAPI), and fluorescence in situ hybridization with a chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were CD45-/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was used to assess the relationship between CTCs, clinical characteristics, and patient outcomes. We detected ≥2 CTCs/3.2 ml whole blood in 43 of 62 patients (69.4%), as well as ≥5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a diagnostic tool; CTCs were associated with tumor burden. CTC levels ≥3/3.2 ml (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2-5.2), p = 0.014) and ≥5/3.2 ml (HR: 3.5, 95% CI: 1.7-7.3, p < 0.001) were both associated with shorter disease-free survival. Moreover, ≥3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2-6.3, p = 0.019) and ≥5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8-8.5, p < 0.001) were predictive of shorter overall survival. CTC assessment may help identify patients with ampullary cancer who are at high risk of an unfavorable outcome.

Application of cryoablation to treat peritoneal carcinomatosis from gastric cancer in a rabbit model.

OBJECTIVES: Peritoneal carcinomatosis is one of the causes of death in patients with advanced gastric cancer. We assumed that cryoablation could be applied as adjuvant therapy to control peritoneal carcinomatosis from gastric cancer. METHODS: We investigated the feasibility of cryoablation technique in rabbit model using a novel cryoablation balloon probe. The cryozones were harvested 7 days after cryoablation for histological evaluation. The levels of cytokines in the peripheral blood of rabbits were also detected. RESULTS: The results demonstrated that cryoablation could be applied in a rabbit model of peritoneal carcinomatosis from gastric cancer. Seven days after cryoablation, necrotic tumor cells could be seen the cryozones. Higher level of IFN-γ was observed. The level of IL-10 was decreased after treatment. CONCLUSIONS: The findings provided the experimental basis for the future application of cryoablation in patients.

Advantages of Early Preventive Ileostomy Closure after Total Mesorectal Excision Surgery for Rectal Cancer: An Institutional Retrospective Study of 123 Consecutive Patients.

BACKGROUND/AIM: Preventive ileostomy is frequently constructed to minimizethe consequences of anastomotic leakage after resection of rectal cancer. There is no consensus regarding the best timing for temporary stoma closure after proctectomy for rectal cancer. This retrospective study sought to determine whether the timing of stoma closure influenced postoperative outcomes. METHODS: Subjects were 123 patients with rectal cancer undergoing laparoscopic or open total mesorectal excision surgery with preventive ileostomy from 2012 to 2015. They were divided into 2 groups according the timing of stoma closure: the standard group who had closure within 90 (60-120) days (n = 78) and the late group who had closure after 180 (150-210) days (n = 45). RESULTS: There was no significant difference in operative time, operative blood loss or postoperative complications between the 2 groups. Timing of postoperative fasting and length of hospital stay was similar in both groups. Adjuvant chemotherapy was not a risk factor for postoperative complications after stoma closure. CONCLUSIONS: There was no significant difference between different timings of temporary stoma closure in relation to postoperative complications. Delayed stoma closure showed no benefit in prevention of morbidity. Early closure is safe and can provide better quality of life for patients.

MiR-622 inhibited colorectal cancer occurrence and metastasis by suppressing K-Ras.

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, with many oncogenes and anti-oncogenes involved. MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules that can adjust downstream targets. Accumulating evidence has revealed that microRNAs govern the occurrence and development of cancer. Here, we studied the role of miR-622 in CRC and clarified the underlying mechanism. We detected that miR-622 was down-regulated in colorectal tumor tissues and cell lines and that miR-622 was lower in metastatic CRC tissues compared with that in non-metastatic specimens. Furthermore, we confirmed that miR-622 inhibited tumor proliferation and migration in vitro. Through dual-luciferase reporter assay, we found kirsten rat sarcoma (K-Ras) gene was the direct target of miR-622. More importantly, K-Ras overexpression can rescue the inhibitory effect of miR-622 on CRC development. All these data were validated in colon xenograft tumor model. MiR-622-K-Ras signal pathway was a potentially new direction in the development of screening target and therapeutic treatments for CRC. © 2015 Wiley Periodicals, Inc.

Clinical safety and outcomes of laparoscopic surgery versus open surgery for palliative resection of primary tumors in patients with stage IV colorectal cancer: a meta-analysis.

BACKGROUND: This study was performed to compare the clinical safety and outcomes of laparoscopic versus open surgery for primary tumors in patients with stage IV colorectal cancer. METHODS: Pertinent studies were selected from the MEDLINE, EMBASE, and Cochrane Library databases; references from published articles; and reviews. Both prospective and retrospective studies were included for the meta-analysis. Clinical outcomes included safety, complications, mortality, and survival. RESULTS: Six trials involving 1802 patients were included. The operative time was longer for laparoscopic than for open surgery (mean difference (MD) = 44.20, 95 % confidence interval (CI) 17.31-71.09, Z = 3.22, P = 0.001). Laparoscopic surgery was also associated with fewer postoperative complications (odds ratio 0.53, 95 % CI 0.37-0.78, Z = 3.29, P = 0.001) and less operative blood loss (MD = -65.40, 95 % CI -102.37 to -28.42, Z = 3.47, P = 0.0005). Median survival ranged from 11.4 to 30.1 months. The total hospital stay was 1.68 days shorter for laparoscopic than for open surgery (95 % CI -1.83 to -1.53, Z = 21.64, P < 0.00001). CONCLUSION: Laparoscopic surgery for palliative resection of stage IV colorectal cancer is associated with better perioperative outcomes than open surgery.

A plasma microRNA panel for early detection of colorectal cancer.

Colonoscopy remains the standard screening method for detecting colorectal cancer (CRC) at an early stage. However, many people avoid having a colonoscopy because of the fear for its potential complications. Our study aimed to identify plasma microRNAs for preliminarily screening CRC in general population, so that some unnecessary colonoscopies can be avoided. We investigated plasma microRNA expression in three independent cohorts including the discovery (n = 80), training (n = 112), and validation (n = 49) phases recruited at two medical centers. Microarrays were used for screening 723 microRNAs in 80 plasma samples to identify candidate microRNAs. Quantitative reverse-transcriptase PCR was performed on the 161 training and validation plasma samples to evaluate the candidate microRNAs discovered from microarrays. A logistic regression model was constructed based on the training cohort and then verified by using the validation dataset. Area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified a panel of miR-409-3p, miR-7, and miR-93 that yielded high diagnostic accuracy in discriminating CRC from healthy group (AUC: 0.866 and 0.897 for training and validation dataset, respectively). Moreover, the diagnostic performance of the microRNA panel persisted in nonmetastasis CRC stages (Dukes' A-B, AUC: 0.809 and 0.892 for training and validation dataset, respectively) and in metastasis CRC stages (Dukes' C-D, AUC: 0.917 and 0.865 for training and validation dataset, respectively). In conclusion, our study reveals a plasma microRNA panel that has potential clinical value in early CRC detection and would play a critical role on preliminarily screening CRC in general population.

MiR-301a promotes colorectal cancer cell growth and invasion by directly targeting SOCS6.

BACKGROUND/AIMS: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and microRNAs play a crucial role in CRC biology. The purpose of this study was to investigate the exact functions and potential mechanisms of action of miR-301a in CRC. METHODS: Quantitative real-time PCR was conducted to assess the expression of miR-301a. Cell proliferation was detected using MTT and colony formation assay, and cell invasion and migration were evaluated using Transwell assay. Luciferase reporter assay was used to identify the direct regulation of suppressor of cytokine signaling 6 (SOCS6) by miR-301a. RESULTS: We first confirmed the upregulation of miR-301a in CRC tissues and cell lines. Gain-of-function and loss-of-function studies in the human CRC cell lines, SW480 and SW620, showed that miR-301a acts as an oncogene by increasing cell proliferation, migration and invasion as well as tumor growth. Furthermore, SOCS6 was identified as a target gene of miR-301a. Reintroduction of SOCS6 partially abrogated miR-301a-induced cell proliferation, migration and invasion. CONCLUSION: These data suggest that miR-301a promotes CRC progression by directly downregulating SOCS6 expression, and miR-301a may represent a novel biomarker for the prevention and treatment of CRC.

Prognostic factors and multidisciplinary treatment modalities for brain metastases from colorectal cancer: analysis of 93 patients.

BACKGROUND: The purpose of this study was to review patient characteristics and evaluate the potential factors affecting prognosis in cases of brain metastasis (BM) from colorectal cancer (CRC). METHODS: We retrospectively reviewed 93 cases of BM from CRC in our hospital. Patient demographics, neurologic symptoms, and location and number of BMs were recorded. Factors analyzed included: age; sex; Karnofsky performance score; number of BMs; presence of extracranial metastases; dimensions; location of tumors; treatment modalities. RESULTS: The overall 1- and 2-year survival rates were 27.7 and 9.9%. On multivariate analysis, the number of BMs, extracranial metastases and the initial treatment modalities were found to be independent prognostic factors for overall survival. Patients treated with surgical resection followed by WBRT or SRS had an improved prognosis relative to those treated with surgery alone (P=0.02 and P=0.02, respectively). No significance difference in survival rate was found between patients treated with SRS alone or SRS plus WBRT (P=0.11). CONCLUSIONS: Surgical resection of BMs from CRC in selected patients may help prolong survival. Additional radiotherapy following surgery is valuable in improving prognosis. Extracranial metastasis, multiple BM lesions and initial non operation can be considered as independent factors associated with poor prognosis.

Dysregulation of over-expressed IL-32 in colorectal cancer induces metastasis.

BACKGROUND: Interleukin (IL)-32 is a described intracellular pluripotent pro-inflammatory mediator, characterized by the signaling of NF-κB and STAT3. METHODS: Our study investigated whether IL-32 expression has clinical significance in the metastases of colorectal cancer (CRC). A total of 70 CRC patients were enrolled, 47 cases of which were single CRC organic metastasis lesions while the rest of which were primary CRC lesions (T4NxM0). IL-32 expression was detected by immunohistochemistry, and the correlation between IL-32 expression and CRC metastases was analyzed. RESULTS: The positive rates of IL-32 in the CRC organic metastasis group were more severe than those in the primary CRC group (P < 0.05). The positive rate of IL-32 in primary CRC with lymph node metastasis was more severe than that of IL-32 in primary CRC without lymph node metastasis (P < 0.05). CONCLUSIONS: The level of IL-32 expression could influence the N grade of CRC. Thus, IL-32 expression may stimulate the organic metastasis and the lymph node metastasis of CRC.

Clinical application of adoptive T cell therapy in solid tumors.

As an emerging therapeutic approach, adoptive T cell therapy shown promise in advanced solid malignancies. The results obtained in patients with metastatic melanoma and kidney cancer are encouraging because of the visible clinical benefits and limited adverse effects. Recently, the genetically-modified T cells expressing specific T cell receptors or chimeric antigen receptors are just now entering the clinical arena and show great potential for high avidity to tumor-associated antigens and long-lasting anti-tumor responses. However, continued investigations are necessary to improve the cell product quality so as to decrease adverse effects and clinical costs, and make adoptive T cell therapy a tool of choice for solid malignancies.

Perioperative mortality and morbidity prediction using POSSUM, P-POSSUM and APACHE II in Chinese gastric cancer patients: surgical method is a key independent factor affecting prognosis.

INTRODUCTION: Gastric cancer is the fourth most common cancer worldwide. Predicting morbidity and mortality is important in deciding timing of surgery and type of surgery offered. APACHE II, POSSUM, and P-POSSUM are the most reliable scoring methods in use today. This is the first paper to evaluate the utility of all three scoring systems in China. METHODS: We collected data on 851 patients (583 male and 268 female) who underwent surgery between 1991 and 2011. Physiological and pathological data was entered in spreadsheet format and analyzed using STATA version 11.0 to generate ROC curves for each scoring system. RESULTS: In predicting mortality, P-POSSUM and POSSUM were most effective and APACHE II was ineffective. POSSUM predicted a higher morbidity risk than was actually encountered. Age and type of operation were found to be independent risk factors for mortality. DISCUSSION: The utility of the APACHE II score in gastric cancer patients is limited. APACHE II is suitable for considering group versus individual effect. The POSSUM score is useful in general surgery, but needs improvement. We found the P-POSSUM score to be superior for morbidity and mortality prediction. P-POSSUM is useful for both the general population and for a specific cohort. The type of surgery is a key decision point for surgeons, and independently affects prognosis. Based upon these findings and clinical scoring systems, clinicians can develop individualized treatment algorithms.

Comparison of clinical safety and outcomes of early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a meta-analysis.

OBJECTIVE: To compare the clinical safety and outcomes of early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy for acute cholecystitis. METHODS: Pertinent studies were selected from the Medline, EMBASE, and Cochrane library databases, references from published articles, and reviews. Seven randomized controlled trials (early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy) were selected. Conventional meta-analysis according to Cochrane Collaboration was used for the pooling of the results. RESULTS: Seven trials with 1106 patients were included. There was no significant difference between the two groups in terms of bile duct injury (Peto odds ratio 0.49 (95% confidence interval 0.05 to 4.72); P = 0.54) or conversion to open cholecystectomy (risk ratio 0.91 (95% confidence interval 0.69 to 1.20); P = 0.50). The total hospital stay was shorter by 4 days for early laparoscopic cholecystectomy (mean difference -4.12 (95% confidence interval -5.22 to -3.03) days; P < 0.00001). CONCLUSION: Early laparoscopic cholecystectomy during acute cholecystitis is safe and shortens the total hospital stay.

Interferon- γ triggers hepatic stellate cell-mediated immune regulation through MEK/ERK signaling pathway.

Hepatic stellate cells (HSCs) interact with immune cells to actively participate in regulating immune response in the liver which is mediated by the effector molecules, including B7-H1. We demonstrated here that expression of B7-H1 on HSCs was markedly enhanced by interferon-(IFN-) γ stimulation. IFN- γ stimulated HSCs inhibited T-cell proliferation via induction of T-cell apoptosis (22.1% ± 1.6%). This immunosuppressive effect was inhibited by preincubation with an anti-B7-H1 antibody, or inhibitor of the MEK/ERK pathway inhibited IFN- γ mediated expression of B7-H1. Thus, regulation of B7-H1 expression on HSCs by IFN- γ represents an important mechanism that regulates immune responses in the liver favoring tolerogenicity rather than immunogenicity. Involvement of MEK/ERK pathway provides a novel target for therapeutic approaches.