Comparison of Centella with Flavonoids for Treatment of Symptoms in Hemorrhoidal Disease and After Surgical Intervention: A Randomized Clinical Trial.

Phlebotonics' effects were evaluated to reduce time-to-stop bleeding and anal irritation in 130 patients who complained of hemorrhoidal disease (HD); bleeding and pain after hemorrhoidectomy (31 patients) and hemorrhoidal thrombosis (34 patients) in the short time. Sixty patients were randomized to receive the routine treatment (both conservative and surgical) (control Group C). The treated group (both conservative and surgical) was divided into two subgroups: one treated with flavonoids (Group A, n = 73), the other with Centella (Group B, n = 66). Time-to-stop bleeding was checked at baseline and checkups (0 up to day 42). Healing was estimated with Kaplan-Meier method, the Kruskal-Wallis test estimated changes in the VAS scores. The HD median time-to-stop bleeding was 2 weeks for Groups A and B; 3 weeks for Group C. VAS scores comparison among Groups (irritation): A vs C, p = 0.007; B vs C, p = 0.041; and A vs B, p = 0.782 resulted respectively. As for operated hemorrhoids, the time-to-stop bleeding was 3 and 4 weeks in Groups A and B and 5 in Group C. Histopathology showed an association between flavonoids and piles' fibrosis (p = 0.008). Phlebotonics in HD, as well as after surgery, showed significant beneficial effects. Flavonoids are the most effective phlebotonics against bleeding and anal irritation.

Comparison of Flavonoids and Centella asiatica for the treatment of chronic anal fissure. A randomized clinical trial.

AIMS: We aim to test and compare the effects of Flavonoids (Fs) and Centella asiatica (Ca), and the traditional treatment to find out which best deals with healing time, bleeding and pain in the treatment of chronic Anal Fissure (AF). Materials of Study: 98 outpatients were divided randomly into treated (either Fs or Ca) and control group. The control group (Group C, n=32) received the traditional treatment along with the other two subgroups which were treated, additionally, with Fs (Group A, n=30) or Ca (Group B, n=36). Patients were observed once weekly over 8 consecutive weeks. RESULTS: The median time to stop bleeding in the group A was 1 week, in the Group B was 3 weeks and in the group C was 4 weeks. There were significant differences between Groups in terms of time to end bleeding (A vs B: p-value= 0.022; A vs C: p-value<0.001; B vs C: p-value=0.070). As for pain score from baseline to the 2nd week were statistically different between Groups A and B on the one hand and Group C on the other hand (A vs C: p-value=0.004; B vs C: p-value 0.035). All patients healed within 8th week. DISCUSSION: Either patients treated with Fs or Ca experienced early pain disappearance. Fs and Ca did not show side effects CONCLUSIONS: The treatment with Fs is the most effective for bleeding. Patients additionally treated with either Fs or Ca experienced an earlier healing and disappearance of pain in comparison with patients underwent to the traditional treatment. KEY WORDS: Anal bleeding, Anal fissure, Defecation pain.

Copper(II) ions affect the gating dynamics of the 20S proteasome: a molecular and in cell study.

Due to their altered metabolism cancer cells are more sensitive to proteasome inhibition or changes of copper levels than normal cells. Thus, the development of copper complexes endowed with proteasome inhibition features has emerged as a promising anticancer strategy. However, limited information is available about the exact mechanism by which copper inhibits proteasome. Here we show that Cu(II) ions simultaneously inhibit the three peptidase activities of isolated 20S proteasomes with potencies (IC50) in the micromolar range. Cu(II) ions, in cell-free conditions, neither catalyze red-ox reactions nor disrupt the assembly of the 20S proteasome but, rather, promote conformational changes associated to impaired channel gating. Notably, HeLa cells grown in a Cu(II)-supplemented medium exhibit decreased proteasome activity. This effect, however, was attenuated in the presence of an antioxidant. Our results suggest that if, on one hand, Cu(II)-inhibited 20S activities may be associated to conformational changes that favor the closed state of the core particle, on the other hand the complex effect induced by Cu(II) ions in cancer cells is the result of several concurring events including ROS-mediated proteasome flooding, and disassembly of the 26S proteasome into its 20S and 19S components.

[The surgical tratment of the subperitoneal rectal cancer]. / Trattamento chirurgico del carcinoma del retto sottoperitoneale.

AIM: To value the results of "open" surgery with sphincter preservation, TME nerve-sparing, fast-track, without a protective stoma in a consecutive series of patients with subperitoneal rectal cancer (s.p.r.c.). MATERIALS AND METHODS: In January 1989, we started a prospective, non-randomized study designed to assess when a primary derivative stoma was warranted in a series of consecutive patients electively treated with open low and ultralow AR. The inclusion criteria were: all patients with middle and low rectal cancer who underwent elective low and ultralow AR, including those treated with neoadjuvant therapy. The exclusion criteria were: urgent surgery, incomplete rings in the stapler, a positive hydropneumatic test, preoperative involvement of the external sphincter and/or surrounding structures by the tumor as demonstrated by CT-scan and endorectal MR and/or transrectal ultrasound. Anastomoses between 7 cm and 4 cm from the pectinate line were defined as low colo-rectal anastomoses, while anastomoses lower than 4 cm from the pectinate line were defined as ultralow anastomoses. A fistula or anastomotic dehiscence was suspected when pelvic and/or peritoneal pain, fever, leucocytosis, fecaloid liquid in the drainage and/or perianal erythematosus swelling were present. An anastomotic leak was confirmed by means of angio-CT and/or endoscopy and/or contrast enema depending on the procedure available most promptly. Signs of peritoneal reaction were considered to be indicative of a major dehiscence, regardless of the diameter of the fistula; when diagnosed, a transverse colostomy was immediately performed. Clinically less serious cases were defined as minor dehiscences, for which a "wait and see" strategy or a transcutaneous CT or ultrasound guided drainage of an abscess were used. Sixty-five patients were treated according to a fast-track postoperative protocol. RESULTS: Between 1998 and 2007, 89 patients with s.p.r.c. were treated according to a prospective protocol. One hundred and nineteen patients (69.6%) underwent low anastomoses and 52 patients (30.4%) underwent ultra low anastomoses. Forty-two (24.6%) were treated with traditional AR, 129 (75.4%) with AR and nerve-sparing TME. Forty-six (26.9%) patients underwent neoadjuvant therapy. One hundred and two patients underwent a mechanical end-to-end anastomosis, 67 a double stapled anastomosis, and 2 a colo-anal anastomosis at the pectinate line performed according to our technique. All 6 patients with major dehiscences underwent a protective colostomy within hours of the onset of clinical symptoms immediately after the radiologically- or endoscopically-confirmed diagnosis. The 7 minor dehiscences were successfully treated with conservative therapy (antibiotic and enteral feeding) using an out-patient regimen. Two (28.6%) required percutaneous drainage: one pelvic CT-guided drainage and the other (an ultralow dehiscence) perineal drainage. The 72.6% of the patients survived at 5-years follow-up. The incidence of local recurrences in 2-years followup was 3.2% (on 124 patients). We had no deaths in patients treated with fast-track protocol. CONCLUSION: Open, TME nerve-sparing A.R. with selective use of neoadjuvant therapy, can be successfully performed without a protective stoma in more than 80% of the patients. Fast-track protocol seems to increase quality of p.o. period and decrease hospital stay