ADAM12 is A Potential Therapeutic Target Regulated by Hypomethylation in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and currently lacks any effective targeted therapy. Since epigenetic alterations are a common event in TNBC, DNA methylation profiling can be useful for identifying potential biomarkers and therapeutic targets. Here, genome-wide DNA methylation from eight TNBC and six non-neoplastic tissues was analysed using Illumina Human Methylation 450K BeadChip. Results were validated by pyrosequencing in an independent cohort of 50 TNBC and 24 non-neoplastic samples, where protein expression was also assessed by immunohistochemistry. The functional role of disintegrin and metalloproteinase domain-containing protein 12(ADAM12) in TNBC cell proliferation, migration and drug response was analysed by gene expression silencing with short hairpin RNA. Three genes (Von Willenbrand factor C and Epidermal Growth Factor domain-containing protein (VWCE), tetraspanin-9 (TSPAN9) and ADAM12) were found to be exclusively hypomethylated in TNBC. Furthermore, ADAM12 hypomethylation was associated with a worse outcome in TNBC tissues and was also found in adjacent-to-tumour tissue and, preliminarily, in plasma from TNBC patients. In addition, ADAM12 silencing decreased TNBC cell proliferation and migration and improved doxorubicin sensitivity in TNBC cells. Our results indicate that ADAM12 is a potential therapeutic target and its hypomethylation could be a poor outcome biomarker in TNBC.

Influence of rescrubbing before laparotomy closure on abdominal wound infection after colorectal cancer surgery: results of a multicenter randomized clinical trial.

OBJECTIVE: To test the hypothesis that strict asepsis in closing wounds following laparotomy reduces the risk for surgical wound infection in elective colorectal cancer surgery. DESIGN: Multicenter randomized clinical trial conducted from June 1, 2009, through June 1, 2010. SETTINGS: Colorectal surgery units of 9 Spanish hospitals. PATIENTS: A total of 969 patients who underwent elective colorectal cancer surgery were eligible for randomization. In closing the laparotomy wound, the patients were randomized to 2 groups: conventional (n=516) and new operation (n=453). In the conventional group, a new set of instruments was used, surgical staff changed their gloves, and the surgical drapes surrounding the laparotomy were covered by a new set of drapes. The new operation group involved removing all drapes, the surgical staff scrubbed again, and a new set of drapes and instruments was used. MAIN OUTCOME MEASURES: Incisional (superficial and deep) surgical site infection 30 days after the operation and risk factors for postoperative wound infections. RESULTS: A total of 146 incisional surgical site infections (15.1%) were diagnosed. Of these, 96 (9.9%) were superficial and 50 (5.1%) were deep infections. On an intent-to-treat basis, significant differences were found between both groups (66 [12.8%] in the conventional group vs 80 [17.7%] in the new operation group [P=.04]). CONCLUSION: This study does not support the use of rescrubbing to reduce the incidence of incisional surgical site infection. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN19463413

Prevalence of symptoms of knee or hip joints in older adults from the general population.

BACKGROUND AND AIMS: The prevalence of knee and hip symptoms varies from study to study, or is unknown. The goals of this study were to determine the prevalence of these symptoms, of diagnosed osteoarthritis and the use of prostheses, by age and gender, in a sample of the general older population. METHODS: We mailed a questionnaire to 11,002 people aged 60 to 90 years who were selected by stratified random sampling. The questionnaire included questions on pain, functional limitations, diagnosed osteoarthritis, previous operations on either or both joints, and sociodemographic data. Descriptive statistics were performed. RESULTS: From 10,150 people who fulfilled the selection criteria, 74.6% answered the questionnaire. Up to 49.2% of the subjects reported pain in either knee or hip or both, with pain in the knee reported more frequently (38.3%) than the hip (23.8%). Functional limitations were present in 51.6% of respondents, with 42.5% having limitations in the knees and 27.7% in the hips. The symptoms increased with age and were more prevalent in women. About 6.6% of respondents reported that they had already had prosthesis implant (hip 3.9%; knee 2.6%). The presence of a hip prosthesis was slightly lower in women than in men and more women had a knee prosthesis. Physicians had already diagnosed osteoarthritis in 38.5% of the sample, 19.4% of the hip and 31% of the knee. CONCLUSIONS: The prevalence of pain symptoms is relatively high among older people, more often in the knee and, in both joints, more often in women, but the rate of prosthetic surgeries was low, which means that additional studies are necessary to gain insight into the healthcare needs of the population.

[Introduction of laparoscopy in the treatment of rectal cancer in a coloproctology unit]. / Introducción de la laparoscopia en el tratamiento del cáncer de recto en una unidad de coloproctología.

INTRODUCTION: The application of the laparoscopic approach to the treatment of rectal cancer is controversial. The aim of the present study was to evaluate whether the introduction of this technique in a coloproctology unit modified the quality of rectal cancer surgery. MATERIAL AND METHOD: We performed a prospective, nonrandomized study of all patients with rectal cancer who underwent surgery with curative intent in 2003 and 2004. Patients with stage T4 tumors were excluded. Of the 59 patients included, 33 underwent laparoscopic surgery and 26 underwent open surgery. A series of intraoperative and postoperative variables and characteristics of the surgical specimen were compared between the two groups. RESULTS: No differences were found between the two groups in the type of intervention performed or in the rate of sphincter preservation. Overall morbidity was 39% in the laparoscopic group and 34% in the open surgery group (NS). Anastomotic dehiscence was 9.5% and 5.8% respectively (NS). The length of hospital stay was similar in both groups. The distal margin was adequate in all patients. The circumferential resection margin was positive (< 1 mm) in 10.7% of patients in the laparoscopic group who underwent total mesorectal excision and in 13.6% of those in the open surgery group (NS). The mean number of isolated nodes was 12.5 in the laparoscopic group and 15.5 in the open surgery group (NS). CONCLUSION: The introduction of the laparoscopic approach in the treatment of rectal cancer in our unit has not lowered surgical quality, as measured by clinical and histopathological variables.

[Incidence of psychiatric disorders in patients with fecal incontinence]. / Incidencia de problemas psiquiátricos en pacientes con incontinencia fecal.

OBJECTIVE: To evaluate the presence of psychiatric alterations in patients with fecal incontinence. PATIENTS AND METHOD: Eighty consecutive patients (67 women) with fecal incontinence were evaluated. All the patients completed the the specific GHQ-28 questionnaire to evaluate psychiatric symptoms. The questionnaire had previously been validated in the Spanish language. A score equal to or higher than 6 points was considered to indicate pathology. Incontinence was evaluated by the Cleveland Clinic Florida-Fecal Incontinence severity score (range 0 - 20). Psychiatric antecedents prior to fecal incontinence were recorded. RESULTS: Thirty-two patients (40%) had pathological scores on the GHQ-28 questionnaire (mean 13.59, range: 7-26). The mean Cleveland score was 11.52 (range: 2-20). Patients with pathological GHQ-28 scores had higher fecal incontinence scores (14.28 vs 9.68; p < 0.0001). A significant lineal correlation was found between GHQ-28 scores and the severity of fecal incontinence (p < 0.0001). Psychiatric antecedents were found in 17 patients (21.3%). In these patients no correlation was found between GHQ-28 score and the severity of incontinence. In the subgroup of patients without psychiatric antecedents this correlation was maintained (p < 0.003). Of these, 20 (31.7%) had pathologic scores on the GHQ-28, and the mean incontinence severity score was significantly higher than that of those with a normal GHQ-28 score (13.15 vs. 9.25; p < 0.004). CONCLUSIONS: The prevalence of psychiatric alterations is high in patients with fecal incontinence and is correlated with its severity. Patients with psychiatric antecedents can bias evaluation of the association between psychiatric alterations and the severity of fecal incontinence.

Stapled hemorrhoidopexy vs. diathermy excision for fourth-degree hemorrhoids: a randomized, clinical trial and review of the literature.

PURPOSE: The aim of this prospective study was to compare the results of stapled hemorrhoidopexy with those of conventional diathermy excision for controlling symptoms in patients with fourth-degree hemorrhoids. METHODS: Thirty-one patients with symptomatic, prolapsed irreducible piles were randomized to either stapled hemorrhoidopexy (n = 15) or diathermy excision (n = 16). The primary outcome measure was the control of hemorrhoidal symptoms one year after operation. RESULTS: The two procedures were comparable in terms of pain relief and disappearance of bleeding. Recurrent prolapse starting from the fourth month after operation was confirmed in 8 of 15 patients in the stapled group and in none in the diathermy excision group: two-tailed Fisher's exact test P = 0.002, RR 0.33, 95 percent confidence interval 0.19-0.59). Five of these patients responded well to a later conventional diathermy hemorrhoidectomy. Persistence of itching was reported in six patients in the stapled group and in one of the diathermy excision group (P = 0.03). On the other hand, six patients in the stapled group and none in the diathermy excision group experienced tenesmus (P = 0.007). CONCLUSIONS: Stapled hemorrhoidopexy was not effective as a definitive cure for the symptoms of prolapse and itching in patients with fourth-degree hemorrhoids. Moreover, stapled hemorrhoidopexy induced the appearance of a new symptom, tenesmus, in 40 percent of the patients. Therefore conventional diathermy hemorrhoidectomy should continue to be recommended in patients with symptomatic, prolapsed, irreducible piles.

[Fissure-in-ano. Alterations in continence and quality of life during disease and at six months after lateral subcutaneous internal sphincterotomy]. / Fisura de ano. Alteraciones de la continencia y de la calidad de vida durante la enfermedad y a los 6 meses de la esfinterotomía lateral interna subcutánea.

OBJECTIVE: To prospectively evaluate alterations in continence and quality of life produced by lateral internal sphincterotomy with each patient acting as his or her own control. PATIENTS AND METHOD: Quality of life (SF-36 questionnaire) and fecal incontinence (Cleveland Clinic Florida-Fecal Incontinence [CCF-FI] questionnaire) were evaluated before and 6 months after lateral internal sphincterotomy was performed in 113 consecutive patients diagnosed with chronic anal fissure. RESULTS: Four patients were excluded because of their inability to complete the SF-36 questionnaire without help. Of the 109 remaining patients, there was persistence or relapse of anal fissure in six (5.5%). One patient refused to complete the quality of life questionnaire again and was excluded from the study. Of the 108 patients who completed the study, the median (interquartile range) score in the CCF-FI scale increased from 0.00 (3) before the intervention to 1(4) in the postoperative period (p = 0.001). Quality of life significantly improved after the operation, since the scores of the following scales increased: physical functioning (p = 0,005), role limitations-physical (p = 0.006), bodily pain (p < 0.001), vitality (p = 0.008), social functioning (p = 0.022) and mental health (p < 0.001). No statistically significant differences were found in general health perception or in role limitations-emotional. CONCLUSION: Despite deterioration in continence, sphincterotomy improves quality of life in patients with anal fissure.