Association of Delayed Surgery With Oncologic Long-term Outcomes in Patients With Locally Advanced Rectal Cancer Not Responding to Preoperative Chemoradiation.

Importance: Extending the interval between the end of neoadjuvant chemoradiotherapy (CRT) and surgery may enhance tumor response in patients with locally advanced rectal cancer. However, data on the association of delaying surgery with long-term outcome in patients who had a minor or poor response are lacking. Objective: To assess a large series of patients who had minor or no tumor response to CRT and the association of shorter or longer waiting times between CRT and surgery with short- and long-term outcomes. Design, Setting, and Participants: This is a multicenter retrospective cohort study. Data from 1701 consecutive patients with rectal cancer treated in 12 Italian referral centers were analyzed for colorectal surgery between January 2000 and December 2014. Patients with a minor or null tumor response (ypT stage of 2 to 3 or ypN positive) stage greater than 0 to neoadjuvant CRT were selected for the study. The data were analyzed between March and July 2020. Exposures: Patients who had a minor or null tumor response were divided into 2 groups according to the wait time between neoadjuvant therapy end and surgery. Differences in surgical and oncological outcomes between these 2 groups were explored. Main Outcomes and Measures: The primary outcomes were overall and disease-free survival between the 2 groups. Results: Of a total of 1064 patients, 654 (61.5%) were male, and the median (IQR) age was 64 (55-71) years. A total of 579 patients (54.4%) had a shorter wait time (8 weeks or less) 485 patients (45.6%) had a longer wait time (greater than 8 weeks). A longer waiting time before surgery was associated with worse 5- and 10-year overall survival rates (67.6% [95% CI, 63.1%-71.7%] vs 80.3% [95% CI, 76.5%-83.6%] at 5 years; 40.1% [95% CI, 33.5%-46.5%] vs 57.8% [95% CI, 52.1%-63.0%] at 10 years; P < .001). Also, delayed surgery was associated with worse 5- and 10-year disease-free survival (59.6% [95% CI, 54.9%-63.9%] vs 72.0% [95% CI, 67.9%-75.7%] at 5 years; 36.2% [95% CI, 29.9%-42.4%] vs 53.9% [95% CI, 48.5%-59.1%] at 10 years; P < .001). At multivariate analysis, a longer waiting time was associated with an augmented risk of death (hazard ratio, 1.84; 95% CI, 1.50-2.26; P < .001) and death/recurrence (hazard ratio, 1.69; 95% CI, 1.39-2.04; P < .001). Conclusions and Relevance: In this cohort study, a longer interval before surgery after completing neoadjuvant CRT was associated with worse overall and disease-free survival in tumors with a poor pathological response to preoperative CRT. Based on these findings, patients who do not respond well to CRT should be identified early after the end of CRT and undergo surgery without delay.

Laparoscopic repair of giant Morgagni hernia by direct suturing with V-Loc.

BACKGROUND: Morgagni hernias present technical challenges. The laparoscopic approach for repair was first described in 1992; however, as these hernias are uncommon in adult life, few data exist on the optimal method for surgical management. The purpose of this study was to analyze a method for laparoscopic repair of Morgagni giant hernias using laparoscopic primary closure with V lock (Medtronic, Covidien). METHODS: This case series describes a method of laparoscopic Morgagni hernia repair using primary closure. In all patients, a laparoscopic transabdominal approach was used. The content of the hernia was reduced into the abdomen, and the diaphragmatic defect was closed with a running laparoscopic suture using a self-fixating suture. Clips were placed at the edges of the suture to secure the pledged sutures to both the anterior and posterior fascia. Demographic data such as BMI and operative and postoperative data were collected. RESULTS: Retrospectively collected data for 9 patients were analyzed. There were 1 (11.1%) males and 8 (88.8%) females. The median BMI was 29.14±52 kg/m2. The median operative time was 80±25 minutes. There were no intraoperative complications or conversions to open surgery. Patients began a fluid diet on the first postoperative day and were discharged after a median hospital stay of 3±1.87 days. In a median follow-up of 36 months, we did not observe any recurrences. CONCLUSIONS: Transabdominal laparoscopic approach with primary closure of the diaphragmatic defect is a viable approach for the repair of Morgagni hernia. In our experience, the use of laparoscopic transabdominal suture fixed to the fascia allowed the closure of the defect laparoscopically with minimal tension on the repairs.

Erratum: Correction of Affiliation.

This corrects the article "Anastomotic healing in a rat model of peritonitis after non-steroidal anti-inflammatory drug administration " in volume 64(1):3085 In the published article "Anastomotic healing in a rat model of peritonitis after non-steroidal anti-inflammatory drug administration" Eur J Histochem 2020;64(1):3085, https://doi.org/10.4081/ejh.2020.3085," one affiliation was published incorrectly. The authors apologize for any inconvenience that it may have caused. Roberto Ghiselli,1 Guendalina Lucarini,2 Monica Ortenzi,1 Eleonora Salvolini,3 Stefania Saccomanno,2 Fiorenza Orlando,4 Mauro Provinciali,4 Fabio Casciani,1 Mario Guerrieri1 1Clinic of Surgery, Marche Polytechnic University, Ancona 2Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona 3Department of Odontostomatologic and Specialized Clinical Sciences, Marche Polytechnic University, Ancona 4Experimental Animal Models for Aging Units, Research Department, Italian National Institute on Aging (INRCA) IRCCS, Ancona, Italy The affiliation should be corrected as follows: 4Experimental Animal Models for Aging Units, Scientific Technological Area, IRCCS INRCA, Ancona, Italy.

Transanal endoscopic microsurgery: indications, tips and long-term results. A single center experience.

BACKGROUND: Transanal endoscopic microsurgery (TEM) was introduced to combine the curativeness of full thickness excision with minimum morbidity, while traditional rectal surgery is burdened by high morbidity and mortality rates. However, while it is still a matter of considerable debate whether local excision is an adequate approach for curative resection of rectal cancer, new minimally invasive operative techniques have been introduced. The purpose of this paper was to show the indications, the tips and long term results of this technique through the review of the largest single-center database available to date. The showed results derived from the single center experience of the Clinica Chirurgica of Polytechnic University of Marche. METHODS: We retrospectively reviewed a 25-year database from May 1992 to May 2017. We divided the patients into three different groups of patients according to the preoperative diagnosis: rectal cancers, adenomas and other rectal lesions. Rectal adenomas were divided into two groups according to their diameter (> or <5 cm). Rectal cancer patients were divided into two groups according to the preoperative staging: early rectal cancer and irradiated rectal cancer. RESULTS: Among the 1324 patients who had rectal tumors excised with TEM at our institution, preoperative histology was rectal adenoma in 729 (55%) patients, adenocarcinoma in 536 (40.5%) patients and other lesions in the remaining 59 (4.4%) patients. 5 years overall survival (OS) and Recurrence free survival (RFS) were 93.3% and 98.6% for patients with rectal adenomas and 86.8% and 70.9% for patients with rectal cancer. CONCLUSIONS: TEM can be a valid alternative for the treatment of both benign and malignant rectal lesions, further studies are needed to define more specific indications to justify the survival of this technique in the future.

Anastomotic healing in a rat model of peritonitis after non-steroidal anti-inflammatory drug administration.

The tissue inflammatory response can influence the outcome of anastomotic healing. Anastomotic leakage represents a dreadful complication after gastrointestinal surgery, in particular sepsis and intra-abdominal infections impair the restorative process of colic anastomoses. It has been debated whether the administration of non-steroidal anti-inflammatory drugs (NSAIDs) is a risk factor for dehiscence, since many patients receive NSAIDs in the early postoperative period. Our aim was, for the first time, to analyze the morpho-functional effects of postoperative administration of two commonly used NSAIDs, Diclofenac and Ketorolac, on the healing process of colo-colic anastomoses constructed under condition of fecal peritonitis in a rat model. Sixty adult male rats underwent two surgical procedures: peritonitis induction and colo-colic anastomosis, and were divided into three groups: 20 rats received saline; 20 rats 4 mg/kg Diclofenac and 20 rats 5 mg/kg Ketorolac. We assessed anastomosis strength, morphological features of tissue wound healing, immunohistochemical metalloproteinase 9 (MMP9) expression and collagen deposition and content by Sirius red staining and hydroxyproline level. We found no significant difference in bursting pressure, collagen content and organization and morphological features between the groups, except a significantly reduced presence of inflammatory cells and MMP9 expression in the groups treated with NSAIDs. Our findings showed that Diclofenac and Ketorolac administration did not affect post-surgical healing and did not increase the leakage risk of colo-colic anastomoses during peritonitis.

Minimally invasive approach to the adrenal gland in obese patients with Cushing's syndrome.

Introduction: The combination of Cushing's syndrome and obesity, one of the most common manifestations of the syndrome itself, may be associated with the worsening of post-operative outcomes in case of laparoscopic adrenalectomy. This study focused on the laparoscopic treatment of Cushing's syndrome with the purpose to identify any relevant difference between morbidly obese, mildly obese and non-obese patients.Material and methods: Patients were retrospectively divided into three groups according to their Body Mass Index (BMI). Demographic characteristics, operative and post-operative data were collected. Data about different hemostatic devices were also collected and compared. Differences were analyzed with the Fisher's exact test for categorical variables, and the Mann-Whitney test for continuous variables.Results: No differences were found in operative time (101.5 ± 50.9 min; p = .919), conversion rate (2.6%; p = .655) or length of stay (4.3 ± 2.9 days; p = .886). Complication rate was 3% (p = .32), without any mortality. 95% of patients showed a complete resolution of hypercotisolyism-related symptoms, and a mean BMI reduction of 5 ± 3.2 kg/m2 (follow up = 6.3 ± 4.2 years). Conclusions: Laparoscopic adrenalectomy is safe and feasible in obese patients affected with Cushing's disease and it can lead to the resolution of the related symptoms.

Is the bipolar vessel sealer device an effective tool in robotic surgery? A retrospective analysis of our experience and a meta-analysis of the literature about different robotic procedures by investigating operative data and post-operative course.

BACKGROUND: The latest robotic bipolar vessel sealing tools have been described to be effective allowing to perform procedures with reduced blood loss and shorter operative times. The aim of this study was to assess the efficacy and reliability of these devices applied in different robotic procedures. MATERIAL AND METHODS: All robotic operations, between 2014 and 2016, were performed using the EndoWrist One VesselSealer (EWO, Intuitive Surgical, Sunnyvale, CA), a bipolar fully wristed device. Data, including age, gender, body mass index (BMI), were collected. Robot docking time, intraoperative blood loss, robot malfunctioning and overall operative time were analyzed. A meta-analysis of the literature was carried out to point the attention to three different parameters (mean blood loss, operating time and hospital stay) trying to identify how different coagulation devices may affect them. RESULTS: In 73 robotic procedures, the mean operative time was 118.2 minutes (75-125 minutes). Mean hospital stay was four days (2-10 days). There were two post-operative complications (2.74%). CONCLUSIONS: The bipolar vessel sealer offers the efficacy of bipolar diathermy and the advantages of a fully wristed instrument. It does not require any change of instruments for coagulation or involvement of the bedside assistant surgeon. These characteristics lead to a reduction in operative time.

Role of Daptomycin on Burn Wound Healing in an Animal Methicillin-Resistant Staphylococcus aureus Infection Model.

Prolonged hospitalization and antibiotic therapy are risk factors for the development of methicillin-resistant Staphylococcus aureus (MRSA) infections in thermal burn patients. We used a rat model to study the in vivo efficacy of daptomycin in the treatment of burn wound infections by S. aureus, and we evaluated the wound healing process through morphological and immunohistochemical analysis. A copper bar heated in boiling water was applied on a paraspinal site of each rat, resulting in two full-thickness burns. A small gauze was placed over each burn and inoculated with 5 × 107 CFU of S. aureus ATCC 43300. The study included two uninfected control groups with and without daptomycin treatment, an infected control group that did not receive any treatment, and two infected groups treated, respectively, with intraperitoneal daptomycin and teicoplanin. The main outcome measures were quantitative culture, histological evaluation of tissue repair, and immunohistochemical expression of wound healing markers: epidermal growth factor receptor (EGFR) and fibroblast growth factor 2 (FGF-2). The highest inhibition of infection was achieved in the group that received daptomycin, which reduced the bacterial load from 107 CFU/ml to about 103 CFU/g (P < 0.01). The groups treated with daptomycin showed better overall healing with epithelialization and significantly higher collagen scores than the other groups, and these findings were also confirmed by immunohistochemical data. In conclusion, our results support the hypothesis that daptomycin is an important modulator of wound repair by possibly reducing hypertrophic burn scar formation.

Surgical treatment of gastric stromal tumors: laparoscopic versus open approach.

AIM: Gastrointestinal stromal tumors (GIST) are quite rare tumors, but yet they are the most common mesenchymal lesions of gastrointestinal tract. Their outmost frequent origin site is stomach and presently surgical resection is the mainstay in the treatment of gastric non metastatic GIST. Their peculiar characteristic of growth and poor metastatic tendency make this tumors particularly prone to be managed by minimally invasive technique. Presenting our experience we want show the feasibility and safeness of laparoscopic approach for gastric GIST and its benefits versus traditional open surgery and pointing out short term and long terms outcomes. PATIENTS AND METHODS: In our series we included 60 patients who underwent surgery for gastric GIST from 2004 to 2014 at Clinica Chirurgica of Università Politecnica delle Marche. Patients were divided in two group according with surgical approach (open or laparoscopic). Criteria of exclusion were metastatic disease and palliative purpose of surgical resection. All patients underwent endoscopic ultrasonography, fine needle aspiration, TC/MRI or PET before surgery. However most of the definitive diagnosis were postoperative. CD117 and CD34 immunohistochemical positivity were considered suggestive for GIST. Tumors were classified in four different prognostic groups according with pathological findings (size and mitotic count) as reported in Fletcher classification. None of the patients received Imatinib before surgery. All patients underwent follow-up with Computerized Tomography (TC) and/or Magnetic Resonance (MRI) repeated every year (mean 51.98 ± 35.68 months). RESULTS: We performed open surgery on 22 patients (36.7%) and laparoscopic wedge resection on 38 patients (63.33%); one of these underwent robotic wedge resection by da the da Vinci® surgical system. The median age at diagnosis was 64 years (range= 45-71). Patients with gastric GIST presented with various symptoms, including fatigue secondary to anemia, intraluminal gastrointestinal bleeding, abdominal pain, abdominal mass, vomiting and syncope. In 26 patients (43.3%) gastric GISTs were detected incidentally during abdominal exploration, endoscopy, or radiologic imaging. Tumor dimensional difference between the two groups was not significant (mean 4.75 cm, range= 2-13). Operation time was significantly lower in laparoscopic approach (82.4 versus 117.8 min). We did not experience of intraoperative or post-operative complications in laparoscopic group. Conversely 4 patients of open group were transfused for anemia. In our series we didn't observe recurrence or metastasis at mean follow up period of (range= 49-120 months). CONCLUSIONS: Laparoscopic surgery is a minimally invasive approach to the treatment of GISTs and offers many advantages such as short hospital stay and low morbidity. In the meantime oncological outcomes of laparoscopy for gastric GIST, assessed as tumor free resection margins and recurrence rate, are comparable to traditional open strategy. KEY WORDS: Gastrointestinal stromal tumors, Laparoscopy, Minimally invasive surgery, Stomach.

Functional outcomes after TEM in patients with complete clinical response after neoadjuvant chemoradiotherapy.

BACKGROUND: In patients who exhibit a complete clinical response after radio-chemotherapy for rectal cancer, the standard surgical approach might constitute overtreatment. The aim of this study is to analyse the outcomes of anorectal function and quality of life after transanal endoscopic microsurgery (TEM) in irradiated patients with complete clinical response. PATIENTS AND METHODS: Between 2007 and 2014, 84 patients who were diagnosed with stage T2-T3-T4 N0 rectal cancer before chemoradiotherapy showed a complete clinical response to neoadjuvant therapy and underwent TEM. All patients were evaluated before and 1 year after TEM using the Cleveland Clinic Florida Fecal Incontinence Score (CCF-FIS) questionnaire to determine the impact of this surgical technique on the degree of faecal continence. To assess the quality of life of patients after surgery, we administered the Fecal Incontinence Quality of Life Scale. RESULTS: Twenty-three patients exhibited a worse incontinence status after surgical intervention (27.4; 95% CI 18.2-38.2). These patients experienced a median positive absolute variation in the CCF-FIS of four points (95% CI 3.5-4.5; p < 0.001). Female sex and age showed a significant correlation with the worsening of continence status. Scores on the Fecal Incontinence Quality of Life Index Scale did not show a significant difference before and after TEM. CONCLUSIONS: TEM may be an alternative treatment for patients with rectal cancer who exhibit a complete clinical response to neoadjuvant chemoradiotherapy because it offers the possibility to achieve a full thickness excision of the rectal wall. TEM also allows the identification of any residual disease and provides optimal quality of life and functional results.

Transanal endoscopic microsurgery in the treatment of large rectal adenomas.

BACKGROUND: Transanal endoscopic microsurgery (TEM) is a minimally invasive technique allowing to excise large rectal adenomas by local approach. This study shows the feasibility and results of a long term experience of TEM applied in this field. METHODS: A retrospective investigation was performed in patients affected by rectal adenomas (5-11 cm in diameter) who had undergone transanal endoscopic microsurgery from 1992 to 2015. A series of 207 patients met the inclusion criteria and were analyzed for characteristics, intraoperative and postoperative results and long-term follow-up. RESULTS: Median age was 71 years (52-83 years). Of the 207 total patients, 77 were women (37.2%) and 130 men (62.8%). Median distance from the anal verge was 8 cm (4-20 cm). Median size was 6 cm, with lesion ranging from 5 to 11 cm in diameter. Median operative time was 57 minutes (42-90 minutes). We observed 17 (8.2%) minor complications and 2 (0.9%) major complication according to the Clavien-Dindo classification. We did not observe any intraoperative or post-operative mortality. Histological examination showed preoperative undiagnosed cancer in 8 (3.8%) cases in which the pathologist revealed adenocarcinoma staged as T1 Sm1 according to the Kikuchi classification. The median follow-up was 115 months (12-288 months). Six recurrences (2.9%), we observed with a median time for recurrence of 14 months. CONCLUSIONS: TEM provides excellent oncological outcomes in the treatment of large benign rectal lesions, ensuring a minimal risk of resection margin infiltration at pathological examination, and is associated with low risk of complications.

Transanal endoscopic microsurgery as optimal option in treatment of rare rectal lesions: A single centre experience.

AIM: To analyze the outcomes of transanal endoscopic microsurgery (TEM) in the treatment of rare rectal condition like mesenchymal tumors, condylomas, endometriosis and melanoma. METHODS: We retrospectively reviewed a twenty-three years database. Fifty-two patients were enrolled in this study. The lesions were considered suitable for TEM if they were within 20 cm from the anus. All of them underwent an accurate preoperative workup consisting in clinical examination, total colonoscopy with biopsies, endoscopic ultrasonography, and pelvic computerized tomography or pelvic magnetic resonance imaging. Operative time, intraoperative complications, rate of conversion, tumor size, postoperative morbidity, mortality, the length of hospital stay, local and distant recurrence were analyzed. RESULTS: Among the 1328 patients treated by TEM in our department, the 52 patients with rectal abnormalities other than adenoma or adenocarcinoma represented 4.4%. There were 30 males (57.7%) and 22 females (42.3%). Mean age was 55 years (median = 60, range = 24-78). This series included 14 (26.9%) gastrointestinal stromal tumors, 21 neuroendocrine tumors (40.4%), 1 ganglioneuroma (1.9%), 2 solitary ulcers in the rectum (3.8%), 6 cases of rectal endometriosis (11.5%), 6 cases of rectal condylomatosis (11.5%) and 2 rectal melanomas (3.8%). Mean lesion diameter was 2.7 cm (median: 4, range: 0.4-8). Mean distance from the anal verge was 9.5 cm (median: 10, range: 4-15). One patient operated for rectal melanoma developed distant metastases and died two years after the operation. We experienced 2 local recurrences (3.8%) with an overall survival equal to 97.6% (95%CI: 95%-99%) at the end of follow-up and a disease free survival of 98% (95%CI: 96%-99%). CONCLUSION: We could conclude that TEM is an important therapeutical option for rectal rare conditions.

Robotic versus laparoscopic right colectomy for cancer: short-term outcomes and influence of Body Mass Index on conversion rate.

BACKGROUND: It is still controversial if the robotic colorectal surgery provides any advantage compared to conventional laparoscopy. We compared the short-term outcomes of robotic right colectomy (RRC) and laparoscopic right colectomy (LRC) and the influence of Body Mass Index (BMI) on each one. METHODS: Between September 2013 and April 2015, 60 LRC and 30 RRC were performed for colorectal cancer in our institution. Comparison was based on quality of surgical procedure, postoperative and oncological outcomes. The BMI was evaluated as a conversion risk factor. RESULTS: A higher surgery time (P<0.001), a higher operative room setting (P<0.001), a lower time of first flatus (P<0.035) and oral feeding recovery (P<0.034) resulted in RRC group. The probability of conversion to open colectomy was higher for LRC group, but not significantly (P=0.659). The conversion rate was higher in obese patients for both procedures (P<0.001). No difference between the two techniques was reported in the obese class with regard to the conversion rate (P=0.282). Both procedures proved acceptable oncological safety. CONCLUSIONS: RRC offers slightly advantages to the LRC with extracorporeal anastomosis, even if it still requests increased time and costs. This study suggested that this difference increases when BMI rises.

Totally robotic vs 3D laparoscopic colectomy: A single centers preliminary experience.

AIM: To compare robotic and three-dimensional (3D) laparoscopic colectomy based on the literature and our preliminary experience. METHODS: This retrospective observational study compared operative measures and postoperative outcomes between laparoscopic 3D and robotic colectomy for cancer. From September 2013 to September 2014, 24 robotic colectomies and 23 3D laparoscopic colectomy were performed at our Department. Data were analyzed and reported both by approach and by colectomy side. Robotic left colectomy (RL) vs laparoscopic 3D left colectomy (LL 3D) and Robotic right colectomy (RR) vs laparoscopic 3D (LR 3D). Rectal cancer procedures were not included. RESULTS: There were 18 RR and 11 LR 3D, 6 RL and 12 LL 3D. As regards LR 3D, extracorporeal anastomosis (EA) was performed in 7 patients and intracorporeal anastomosis (IA) in 4; the RR group included 14 IA and 4 EA. There was no mortality. Median operative time was higher for the robotic group while conversion rate (12.5% vs 13%) and lymph nodes removed (14 vs 13) were similar for both. First flatus time was 1 d for RR and 2 d the other patient groups. Oral intake was resumed in 1 d by LR and in 2 d by the other patients (P = 0.012). Overall cost was €4950 and €1950 for RL and LL 3D, and €4450 and €1450 for RR and LR 3D, respectively. CONCLUSION: There were no differences between RR and LR 3D, except that IA was easier with RR, and probably contributed with the learning curve to the longer operative time recorded. Both techniques offer similar advantages for the patient with significantly different costs. In left colectomies robotic colectomy provided better outcomes, especially in resections approaching the rectum.

Treatment of rectal cancer by transanal endoscopic microsurgery: experience with 425 patients.

AIM: To describe our experience in treating rectal cancer by transanal endoscopic microsurgery (TEM), report morbidity and mortality and oncological outcome. METHODS: A total of 425 patients with rectal cancer (120 T1, 185 T2, 120 T3 lesions) were staged by digital rectal examination, rectoscopy, transanal endosonography, magnetic resonance imaging and/or computed tomography. Patients with T1-N0 lesions and favourable histological features underwent TEM immediately. Patients with preoperative stage T2-T3-N0 underwent preoperative high-dose radiotherapy; from 1997 those aged less than 70 years and in good general health also underwent preoperative chemotherapy. Patients with T2-T3-N0 lesions were restaged 30 d after radiotherapy and were then operated on 40-50 d after neoadjuvant therapy. The instrumentation designed by Buess was used for all procedures. RESULTS: There were neither perioperative mortality nor intraoperative complications. Conversion to other surgical procedures was never required. Major complications (urethral lesions, perianal or retroperitoneal phlegmon and rectovaginal fistula) occurred in six (1.4%) patients and minor complications (partial suture line dehiscence, stool incontinence and rectal haemorrhage) in 42 (9.9%). Postoperative pain was minimal. Definitive histological examination of the 425 malignant lesions showed 80 (18.8%) pT0, 153 (36%) pT1, 151 (35.5%) pT2, and 41 (9.6%) pT3 lesions. Eighteen (4.2%) patients (ten pT2 and eight pT3) had a local recurrence and 16 (3.8%) had distant metastasis. Cancer-specific survival rates at the end of follow-up were 100% for pT1 patients (253 mo), 93% for pT2 patients (255 mo) and 89% for pT3 patients (239 mo). CONCLUSION: TEM is a safe and effective procedure to treat rectal cancer in selected patients without evidence of nodal involvement. T2-T3 lesions require preoperative neoadjuvant therapy.

Therapeutic efficacy of buforin II and rifampin in a rat model of Acinetobacter baumannii sepsis.

OBJECTIVE: To investigate the efficacy of buforin II and rifampin in an experimental rat model of Acinetobacter baumannii sepsis. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: The animals received intraperitoneally 1 mL saline containing 2 x 10 colony forming units of A. baumannii ATCC 19606 (model i) or the multiresistant strain (model ii). Immediately after bacterial challenge, animals received intravenously a single dose of isotonic sodium chloride solution (control groups C1 and C2), 1 mg/kg of buforin II, 10 mg/kg of rifampin, and 1 mg/kg of buforin II plus 10 mg/kg of rifampin, respectively. MEASUREMENTS AND MAIN RESULTS: Lethality, bacterial growth in blood and tissue burden, endotoxin, interleukin-6, and tumor necrosis factor-alpha concentrations in plasma. Buforin II showed good antimicrobial activity and achieved a significant reduction of plasma endotoxin and cytokines concentration when compared with control and rifampin-treated groups. Combination among buforin II proved to be the most effective treatment in reducing all variables measured. CONCLUSION: In an experimental model, buforin II and rifampin might have a potential role in the treatment of severe infections due to A. baumannii.

Protective effects of the combination of alpha-helical antimicrobial peptides and rifampicin in three rat models of Pseudomonas aeruginosa infection.

INTRODUCTION: An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of magainin II and cecropin A with or without rifampicin against control and multidrug-resistant Pseudomonas aeruginosa strains. METHODS: In vitro experiments included MIC determinations and synergy studies. For in vivo studies, animals were given an intraperitoneal injection of P. aeruginosa lipopolysaccharide, P. aeruginosa ATCC 27853 and one clinical multiresistant P. aeruginosa strain. Groups of animals received intravenously isotonic sodium chloride solution, 10 mg/kg rifampicin, 1 mg/kg magainin II or 1 mg/kg cecropin A. Two groups of animals received a combined treatment with magainin II + rifampicin or cecropin A + rifampicin at the same dosages as the singly treated groups. In addition, a further group was treated with tazobactam/piperacillin (120 mg/kg). Lethality, bacterial growth in blood and peritoneum, and endotoxin and TNF-alpha concentrations in plasma were evaluated. RESULTS: Combinations of alpha-helical antimicrobial peptides showed in vitro synergistic interaction. Magainin II and cecropin A exerted strong antimicrobial activity and achieved a significant reduction in plasma endotoxin and TNF-alpha concentrations when compared with control and rifampicin-treated groups. Rifampicin exhibited no anti-P. aeruginosa activity and good substantial impact on endotoxin and TNF-alpha plasma concentrations. Combined treatment groups had significant reductions in bacterial count, positive blood cultures and mortality rates when compared with singly treated and control groups. CONCLUSIONS: Our results highlight the potential usefulness of these combinations that provide future therapeutic alternatives in P. aeruginosa infections.

Efficacy of the combination of tachyplesin III and clarithromycin in rat models of Escherichia coli sepsis.

We investigated the efficacy of tachyplesin III and clarithromycin in two experimental rat models of severe gram-negative bacterial infections. Adult male Wistar rats were given either (i) an intraperitoneal injection of 1 mg/kg Escherichia coli 0111:B4 lipopolysaccharide or (ii) 2 x 10(10) CFU of E. coli ATCC 25922. For each model, the animals received isotonic sodium chloride solution, 1 mg/kg tachyplesin III, 50 mg/kg clarithromycin, or 1 mg/kg tachyplesin III combined with 50 mg/kg clarithromycin intraperitoneally. Lethality, bacterial growth in the blood and peritoneum, and the concentrations of endotoxin and tumor necrosis factor alpha (TNF-alpha) in plasma were evaluated. All the compounds reduced the lethality of the infections compared to that for the controls. Tachyplesin III exerted a strong antimicrobial activity and achieved a significant reduction of endotoxin and TNF-alpha concentrations in plasma compared to those of the control and clarithromycin-treated groups. Clarithromycin exhibited no antimicrobial activity but had a good impact on endotoxin and TNF-alpha plasma concentrations. A combination of tachyplesin III and clarithromycin resulted in significant reductions in bacterial counts and proved to be the most-effective treatment in reducing all variables measured.