Heat shock protein 27 influences the anti-cancer effect of curcumin in colon cancer cells through ROS production and autophagy activation.

The problem of therapeutic resistance and chemotherapeutic efficacy is tricky and critical in the management of colorectal cancer (CRC). Curcumin is a promising anti-cancer agent. Heat shock protein 27 (HSP27) is correlated with CRC progression and is said to affect CRC response to different therapies. However, the role of HSP27 on the therapeutic efficacy of curcumin remains unknown. HSP27 was silenced using small hairpin RNA (shRNA) technique. The cytotoxic and apoptotic effects of curcumin were assessed by sulforhodamine B (SRB) colorimetric assay, flow cytometric cell cycle analysis, and annexin V/propidium iodide (PI) double-labeling assays. Total reactive oxygen species (ROS)/superoxide and autophagy detection were performed, and the levels of apoptosis-related proteins were examined by Western blotting. It was found that the silencing of HSP27 (HSP27-KD) resulted in increased treatment resistance to curcumin in CRC cells. In addition, cell cycle analysis showed that the curcumin treatment caused cell cycle arrest at the G2/M phase in the control group, and apoptosis was reduced in the HSP27-KD group. Curcumin treatment also resulted in a decrease in anti-apoptotic proteins, p-Akt, Akt, Bcl-2 and p-Bad, and increase in pro-apoptotic proteins Bad and c-PARP levels in the control cells but not in the HSP27-KD cells. This was also followed by low reactive oxygen/nitrogen species (ROS/RNS), superoxide and autophagy induction levels in the HSP27-KD cells as compared to the control cells. Therefore, as silencing of HSP27 increases curcumin resistance by reducing apoptosis and reactive oxidative stress production, HSP27 is a potential selective target for curcumin treatment in CRC.

Single-incision versus conventional laparoscopic appendectomy in 688 patients: a retrospective comparative analysis.

BACKGROUND: Laparoscopic surgery has become the standard for treating appendicitis. The cosmetic benefits of using single-incision laparoscopy are well known, but its duration, complications and time to recovery have not been well documented. We compared 2 laparoscopic approaches for treating appendicitis and evaluated postoperative pain, complications and time to full recovery. METHODS: We retrospectively reviewed the cases of consecutive patients with appendicitis and compared those who underwent conventional laparoscopic appendectomy (CLA) performed using 3 incisions and those who underwent single-incision laparoscopic appendectomy (SILA). During SILA, the single port was prepared to increase visibility of the operative site. RESULTS: Our analysis included 688 consecutive patients: 618 who underwent CLA and 70 who underwent SILA. Postsurgical complications occurred more frequently in the CLA than the SILA group (18.1% v. 7.1%, p = 0.018). Patients who underwent SILA returned to oral feeding sooner than those who underwent CLA (median 12 h v. 22 h, p < 0.001). These between-group differences remained significant after controlling for other factors. Direct comparison of only nonperforated cases, which was determined by pathological examination, revealed that SILA was significantly longer than CLA (60 min v. 50 min, p < 0.001). Patients who underwent SILA had longer in-hospital stays than those who underwent CLA (72 v. 55 h, p < 0.001); however, they had significantly fewer complications (3.0% v. 14.4%, p = 0.006). CONCLUSION: In addition to its cosmetic advantages, SILA led to rapid recovery and no increase in postsurgical pain or complications.

CONTEXTE: La chirurgie laparoscopique est devenue la norme pour le traitement de l'appendicite. Les avantages de la laparoscopie à simple incision au plan esthétique sont bien connus, mais la durée de l'intervention, ses complications et le temps de récupération n'ont pas été adéquatement documentés. Nous avons comparé 2 approches laparoscopiques pour le traitement de l'appendicite et évalué la douleur et les complications postopératoires, de même que le temps de récupération complète. MÉTHODES: Nous avons passé en revue de manière rétrospective les dossiers de patients consécutifs atteints d'appendicite et comparé ceux qui ont subi une appendicectomie laparoscopique classique (ALC) à 3 incisions à ceux qui ont subi une appendicectomie laparoscopique à simple incision (ALSI). Durant l'ALSI, l'incision était préparée de manière à améliorer la visibilité du champ opératoire. RÉSULTATS: Notre analyse a inclus 688 patients consécutifs : 618 qui ont subi une ALC et 70, une ALSI. Les complications postopératoires ont été plus nombreuses dans le groupe soumis à l'ALC qu'à l'ALSI (18,1 % c. 7,1 %, p = 0,018). Les patients soumis à l'ALSI ont repris l'alimentation orale plus rapidement que ceux qui avaient subi une ALC (temps médian 12 h c. 22 h, p < 0,001). Ces différences entre les groupes sont demeurées significatives après incorporation d'autres facteurs. La comparaison directe des cas non perforés seulement, révélés par l'examen anatomopathologique, a révélé que l'ALSI a demandé significativement plus de temps que l'ALC (60 min c. 50 min, p < 0,001). Les patients soumis à l'ALSI ont séjourné plus longtemps à l'hôpital que les patients soumis à l'ALC (72 h c. 55 h, p < 0,001); toutefois, ils ont présenté significativement moins de complications (3,0 % c. 14,4 %, p = 0,006). CONCLUSION: En plus de ses avantages au plan esthétique, l'ALSI a permis une récupération rapide, sans accroissement de la douleur ou des complications postopératoires.

Adjunctive traditional Chinese medicine therapy improves survival in patients with advanced breast cancer: a population-based study.

BACKGROUND: Traditional Chinese medicine (TCM) is one of the most common complementary and alternative medicines used in the treatment of patients with breast cancer. However, the clinical effect of TCM on survival, which is a major concern in these individuals, lacks evidence from large-scale clinical studies. METHODS: The authors used the Taiwan National Health Insurance Research Database to conduct a retrospective population-based cohort study of patients with advanced breast cancer between 2001 and 2010. The patients were separated into TCM users and nonusers, and Cox regression models were applied to determine the association between the use of TCM and patient survival. RESULTS: A total of 729 patients with advanced breast cancer receiving taxanes were included in the current study. Of this cohort, the mean age was 52.0 years; 115 patients were TCM users (15.8%) and 614 patients were TCM nonusers. The mean follow-up was 2.8 years, with 277 deaths reported to occur during the 10-year period. Multivariate analysis demonstrated that, compared with nonusers, the use of TCM was associated with a significantly decreased risk of all-cause mortality (adjusted hazards ratio [HR], 0.55 [95% confidence interval, 0.33-0.90] for TCM use of 30-180 days; adjusted HR, 0.46 [95% confidence interval, 0.27-0.78] for TCM use of >180 days). Among the frequently used TCMs, those found to be most effective (lowest HRs) in reducing mortality were Bai Hua She She Cao, Ban Zhi Lian, and Huang Qi. CONCLUSIONS: The results of the current observational study suggest that adjunctive TCM therapy may lower the risk of death in patients with advanced breast cancer. Future randomized controlled trials are required to validate these findings.

MicroRNA-200a/b influenced the therapeutic effects of curcumin in hepatocellular carcinoma (HCC) cells.

MicroRNAs (miRNAs) play an essential role in regulating gene expression in normal and malignant cells. Expression of the microRNA-200 (miR-200) family has been correlated with malignancy in cancers. However, whether miR-200a/b plays a role in curcumin-mediated treatment of hepatocellular carcinoma (HCC) is unknown. We performed miRNA array analyses in two different HCC cell lines (HepG2 and HepJ5). The expression patterns of miR-200 family members were assessed with real-time PCR. We overexpressed miR-200 family members using a lentiviral system and selected stably transduced clones with antibiotics. The anticancer effects of curcumin on J5-200a, J5-200b, and J5-control cells were assessed by MTT assay, flow cytometry cell cycle analysis, and TUNEL assay. We found that HepG2 cells, which were more resistant to curcumin treatment than HepJ5 cells, expressed higher levels of miR-200a/b. The MTT assay revealed that the overexpression of miR-200a/b in HepJ5 cells conferred enhanced resistance to curcumin treatment compared with the control cells. By cell cycle analysis and TUNEL assay, we found that apoptosis was increased dramatically in J5-control cells compared with J5-200a and J5-200b cells after curcumin treatment. Finally, we evaluated the levels of Bcl-2, Bax, and Bad, and found a decrease of Bcl-2 levels and increase of Bad levels in the J5-control cells treated with curcumin. The expression levels of miR-200a/b might determine the therapeutic efficacy of curcumin on HCC cells.

Intersphincteric resection for very low rectal cancer: clinical outcomes of open versus laparoscopic approach and multidimensional analysis of the learning curve for laparoscopic surgery.

BACKGROUND: Laparoscopic rectal cancer surgery is regarded as more complex because of its technical difficulties in pelvic exposure, dissection, and sphincter preservation. This study therefore aimed to investigate the feasibility of laparoscopic resection for low rectal cancer using intersphincteric resection (ISR) and to assess its short-term oncological outcomes. Further, we intended to analyze the learning curve for laparoscopic surgery and identify the factors influencing the learning curve. METHODS: Patients with low rectal cancer who received open or laparoscopic ISR were retrospectively chart reviewed. The surgical and oncological outcomes were evaluated. Comparisons of operating time, estimated blood loss, surgical outcomes, and histopathologic status were analyzed. Also, operating time was used as a technical indicator for learning curve analysis. RESULTS: The mean estimated blood loss was 265 mL (range, 100-800 mL) in the open group and 104 mL (range, 30-250 mL) in the laparoscopic group. There was a significant difference between these two groups (P < 0.001). Operative experience analysis showed that the mean operating time was 402.1 min (range, 210-570 min) in the first stage and 331.4 min (range, 210-450 min) in the second stage, and on pathologic examination the mean number of lymph nodes harvested was 11.1 (range, 5-21) in the first stage and 18.3 (range, 11-31) in the second stage, with statistical differences between these two stages (P = 0.034 and P = 0.004, respectively). Multifactorial analysis showed that operating time was associated with surgeons' experience (<18 or ≥18 cases) (odds ratio = 2.918, 95% CI 1.078-7.902). Protective stoma creation was also associated with surgeons' experience (odds ratio = 3.999, 95% CI 1.153-13.86). CONCLUSIONS: Our data show that laparoscopic ISR for low rectal cancer is feasible and safe. Surgeons' experience improved operating time and postoperative complications.

Preservation versus division of ilioinguinal nerve on open mesh repair of inguinal hernia: a meta-analysis of randomized controlled trials.

BACKGROUND: Chronic groin pain after inguinal hernia repair, a serious problem, is caused by entrapment of the ilioinguinal nerve either by mesh or development of fibrosis. Division of the ilioinguinal nerve during hernioplasty has been found to reduce the incidence of chronic groin pain. However, the traditional approach favors preservation of the ilioinguinal nerve during open hernia repair. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials that compared the outcomes of preservation versus division of the ilioinguinal nerve during open mesh repair of inguinal hernia. The primary outcome was the incidence of groin pain; secondary outcomes were numbness and sensory loss. RESULTS: We reviewed six trials with 1,286 patients. We found no difference between the groups for the incidence of groin pain or numbness at 1, 6, and 12 months after open mesh inguinal repair. The incidence of sensory loss or change was significantly higher in the division group than in the preservation group at 6 months [risk ratio (RR) 1.25; 95 % confidence interval (CI) 1.02-1.53] and at 12 months (RR 1.55; 95 % CI 1.01-2.37) postoperatively. No significant differences between the groups were noted at any other points in time. CONCLUSIONS: Preservation of the ilioinguinal nerve during open mesh repair of inguinal hernia is associated with a decreased incidence of sensory loss at 6 and 12 months postoperatively compared with that of the division technique. No significant differences were found between the groups for chronic groin pain or numbness.

Acute appendicitis and adverse pregnancy outcomes: a nationwide population-based study.

BACKGROUND/OBJECTIVE: Acute appendicitis is the most common non-obstetric surgical procedure in pregnant women. Using two large-scale nationwide population-based datasets, this study aimed to assess the risk of adverse pregnancy outcomes between mothers with and without appendicitis in Taiwan. METHODS: This study used two nationwide population-based datasets: the Taiwan National Health Insurance Research Dataset and the Taiwan national birth certificate registry. This study included 908 women who had live singleton births and who had been hospitalized with a diagnosis of acute appendicitis, and another randomly selected 4,540 women as a comparison group. Conditional logistic regression analyses were performed to calculate the risk of adverse pregnancy outcomes including low birth weight (LBW), preterm birth, small for gestational age (SGA), cesarean section (CS), congenital anomalies, Apgar scores at 5 min (<7), and pre-eclampsia/eclampsia. RESULTS: The adjusted odds ratios for LBW, preterm birth, SGA, CS, and congenital anomalies in women with acute appendicitis were 1.82 (95 % CI = 1.43-2.30), 1.59 (95 % CI = 1.25-2.02), 1.33 (95 % CI = 1.12-1.60), 1.24 (95 % CI = 1.07-1.44), and 2.07 (95 % CI = 1.07-4.03), respectively, compared with women without acute appendicitis after adjusting for highest maternal educational level, marital status, geographic region, gestational diabetes, gestational hypertension, coronary heart disease, anemia, hyperlipidemia, obesity, and alcohol abuse/alcohol dependence syndrome, infant sex and parity, and paternal age. CONCLUSIONS: There were increased risks for having LBW, preterm infants, SGA, congenital anomalies, and for experiencing CS among women with acute appendicitis than comparison women.

Can we predict pathologic complete response before surgery for locally advanced rectal cancer treated with preoperative chemoradiation therapy?

BACKGROUND: Pathologic complete response has been proven to have oncological benefits for locally advanced rectal cancer treated with chemoradiation therapy. The aims of this study are to analyze and determine the factors to predict pathologic complete response for patients treated with preoperative neoadjuvant therapy. METHODS: Patients with biopsy-proven, locally advanced rectal cancer were treated neoadjuvantly followed by radical surgical resection. Tumors were re-assessed after completing chemoradiation, including pelvic magnetic resonance images, colonoscopic examination, and re-biopsy. The results of examination were compared with the final pathologic status. RESULTS: A retrospective chart review of 166 patients was conducted. Twenty-five patients (15.1%) had pathologic complete response after chemoradiation. The 5-year overall survival rates were better in the complete response group than the residual tumor group (91.1% vs. 70.8%; P = 0.047), and there were also significant differences in the 5-year disease-free survival rates between these two groups (91.1% vs. 70.2%; P = 0.027). The prediction rates for pathologic complete response by re-biopsy, magnetic resonance images, and colonoscopy were 21.4%, 33.3%, and 53.8%, respectively. In addition, when we further combine the results of colonoscopic findings and re-biopsy, the prediction rate for pathologic complete response reached 77.8% (P = 0.009). CONCLUSIONS: Combining the results of the re-biopsy and post-treatment colonoscopic findings, we can achieve a good prediction rate for pathologic complete response. Post-treatment magnetic resonance images are not useful tools in predicting tumor clearance following chemoradiation.

Oncological and functional outcomes of intersphincteric resection for low rectal cancer.

BACKGROUND: The intersphincteric resection technique has been used to extend the opportunity for sphincter preservation in patients with very low rectal cancer. The aim of this study is to assess the long-term oncological and functional outcomes of intersphincteric resection. METHODS: Patients with extraperitoneal rectal cancer were treated and retrospectively chart reviewed. The oncological and functional outcomes were evaluated. Comparisons of the overall disease-free survival and recurrence were analyzed for the different surgical procedures. RESULTS: From July 2002 to August 2009, 162 patients with extraperitoneal rectal cancer were retrospectively chart reviewed. One-hundred one patients (62.3%) underwent low anterior resection, 26 patients (16%) received radical proctectomy and intersphincteric resection with coloanal anastomosis, and 23 (14.2%) had abdominoperineal resection. The sphincter preservation rate was 80%. In the intersphincteric resection group, overall survival rates at 3 and 5 y were 83% and 83%, and disease-free survival at 3 and 5 y were 82% and 76%, respectively. The mean stool frequency was 4.7 per 24 h. There were 38.1% of patients suffering from stool fragmentation, and 23.8% had nocturnal defecation. About one-third of the patients required antidiarrheal medications. Overall, 90.8% of patients were satisfied with the functional results of surgery. CONCLUSIONS: Our data show intersphincteric resection for low rectal cancer is feasible and safe. Preoperative radiotherapy may negatively affect symptom-specific quality of life.

Appendix diameter: a predictor of wound infection after laparoscopic appendectomy.

Our aim was to investigate whether appendix diameter is an independent risk factor for wound infection in laparoscopic appendectomy (LA). Patients who underwent LA (n = 582) were grouped into those with wound infections and those without. Possible factors associated with wound infection were analyzed using univariate and multivariate logistic regression analysis. When the diameter of the appendix was greater than 15 mm, patients were 2.32 times as likely to have a wound infection (95% CI, 1.02 to 5.29; P = 0.045) than if the appendix was less than 10 mm in diameter. Patients with perforated appendices were 2.51 times as likely to have a wound infection (95% CI, 1.25 to 5.02; P = 0.010) than if the appendix was not perforated. Wound infection was associated with longer operation time, return to oral intake, and hospital stay. Appendix diameter may predict postoperative wound infection after laparoscopic appendectomy.

Glucose-regulated protein 78 (GRP78) mediated the efficacy to curcumin treatment on hepatocellular carcinoma.

BACKGROUND: Glucose-regulated protein 78 (GRP78) plays an important role in the therapeutic treatment and progression of cancer. However, little is known about the effect of GRP78 expression to curcumin in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this study, we generated GRP78 knockdown cells (GRP78KD) by a short interfering RNA (siRNA) technique. The antiproliferation effects of curcumin were determined by MTT assay, TUNEL assay, and cell cycle determination. RESULTS: We found that GRP78KD cells were more resistant to curcumin treatment compared with the parental cells in MTT assay. The apoptosis cell population was increased in scrambled-siRNA cells treated with curcumin compared with GRP78KD cells in cell cycle distribution and TUNEL assays. Finally, we found that knocking down GRP78 causes resistance to curcumin treatment through the suppression of caspase-3 and caspase-8 expression levels. CONCLUSIONS: We conclude that the expression level of GRP78 may contribute to the therapeutic effect of curcumin on HCC cells.

Outcomes of staple fixation of mesh versus nonfixation in laparoscopic total extraperitoneal inguinal repair: a meta-analysis of randomized controlled trials.

BACKGROUND: Staple fixation of mesh during laparoscopic total extraperitoneal (TEP) inguinal repair is thought to be necessary to prevent recurrence. However, mesh fixation may increase surgical complications and pain. Therefore, a meta-analysis of randomized controlled trials (RCTs) was conducted to compare the outcomes of nonfixation with fixation of mesh by metal tacks during TEP inguinal hernia repair. METHODS: The meta-analysis was conducted according to the Quality of Reporting of Meta-analyses (QUOROM) standards. The inclusion criteria were RCTs comparing stapled with unstapled mesh in TEP inguinal hernia repair. The primary outcome was incidence of recurrence, secondary outcomes were operative duration, postoperative pain score, number of analgesics consumed, in-hospital stay, time to return to normal activity, cost, and complications. RESULTS: Six trials were included with a total number of 932 patients (1086 hernias): the mesh was fixed in 463 (540 hernias) patients and not fixed in 469 (546 hernias). We found no difference between groups in the incidence of recurrence (OR = 2.01, 95% CI: 0.37-11.02), complications (OR = 0.73, 95% CI: 0.51-1.05), postoperative pain score [day 1 (p = 0.19), day 7 (p = 0.18) and month 1 (p = 0.47)] and number of analgesics consumed (WMD of -1.20, 95% CI: -3.08 to 0.68). The mean operative time (WMD of -3.86, 95% CI: -7.45 to -0.26) and hospital stay (WMD of -0.34, 95% CI: -0.50 to -0.18) were significantly higher in the mesh fixation group. Moreover, a net cost savings was realized for each hernia repair performed without stapled mesh. CONCLUSIONS: Elimination of tack fixation of mesh in TEP inguinal hernia repair is associated with decreased operative cost and significantly reduce operative time and in-hospital stay, but no difference in the risk of hernia recurrence, complications, and postoperative pain. For more detailed evaluation, further well-structured trials with improved standardization of hernia type, operative technique, and surgeon experience are necessary.