Topical treatment of anal condylomata with Propionibacterium acnes lysate: results of a multicentric observational study.

BACKGROUND: Condylomata are a manifestation of HPV infection of the ano-genital epithelium. Recurrence is frequent after any type of treatment (from 20% up to 50%). We assessed the use of a gel containing panthenol, tocopheryl acetate and Propionibacterium extract in the treatment of anal warts. METHODS: Enrollment period was from January 15 to June 15, 2018. Main exclusion criteria were immunodepression, extensive condylomatosis and other treatments (topical/ablative) in the previous six months. RESULTS: Seventy-nine patients were included. Median age was 33 years (19-65), 72.2% were males. Median number of partners and symptoms duration were 6 (1-98) and 3 months (1-18), respectively. Almost all cases had perianal disease (97.5%), while endoanal warts were present in 51.9% of cases. After 30 days of treatment, complete regression occurred in 17 (21.5%) patients, while partial or absent response was reported in 36 (45.6%) and 26 (32.9%) cases, respectively. Forty-seven (59.5%) patients underwent a second month of topical therapy. After a 6-month follow-up, complete or partial response was reported in 53 (67.1%) patients, while in 26 (32.9%) cases the disease remained stable or even worsened. Nineteen (24.1%) patients required cryotherapy, 23 (29.1%) surgical excision, while 2 (2.5%) needed both cryotherapy and surgery. Absence of clinical response was associated with a number of partners ≥10 and symptoms duration of 6 months or shorter (P<0.001 and P=0.050). CONCLUSIONS: In our study, the gel containing P. acnes lysate was a safe topical treatment for perianal and endoanal condylomata and could help to overcome HPV infection. A high number of partners and short symptoms duration appeared to worsen the outcome.

Intracorporeal or extracorporeal ileocolic anastomosis after laparoscopic right colectomy: cost analysis of the Torino trial.

BACKGROUND: Intracorporeal (IIA) and extracorporeal anastomosis (EIA) are two well-established techniques for restoration of bowel continuity after laparoscopic right colectomy (LRC). Since no economic analysis comparing the two different anastomotic techniques has been performed yet, it is still unclear if IIA can reduce perioperative costs. The aim of the study was to compare costs of LRC with IIA or EIA for right-sided colon neoplasm. METHODS: This is a cost analysis of a single-institution double-blinded randomized controlled trial comparing the outcomes of LRC with IIA and LRC with EIA in patients with a right-sided colon neoplasm. All direct in-hospital costs related to patient's admission were recorded (intraoperative costs: operative room, surgical tools, blood units-postoperative costs: hospital stay, laboratory and microbiology analyses, diagnostic services, analgesic drugs and antibiotic therapy, blood units, reoperation-outpatient costs: post-discharge wound medications). This trial was registered with ClinicalTrials.gov, Number NCT03045107. RESULTS: A total of 140 patients were randomized and analyzed. Mean overall costs in the IIA group exceeded 349 € the mean overall costs of the EIA group (7926.87 ± 4617.23 € vs. 7577.45 ± 6131.17 €; P = 0.704). A mean extra charge of 608 € regarding total intraoperative costs was recorded in the IIA group (3058.84 ± 897.42 € vs. 2450.15 ± 558.90 €; P < 0.001). The cost of surgical instruments resulted in 542 € additional charge per patient in the IIA group compared to EIA group (1782.74 ± 541.26 € vs. 1240.55 ± 384.09 €; P < 0.001). The mean cost of operative room occupancy was comparable in IIA and EIA group: 1276.09 ± 514.94 € vs. 1209.60 ± 422.80 € (P = 0.405). No significant differences were observed in postoperative costs and in outpatient costs. CONCLUSION: This economic analysis showed that IIA and EIA after LRC had similar overall costs, even though there were intraoperative extra costs of IIA.

Risk factors for Low Anterior Resection Syndrome (LARS) in patients undergoing laparoscopic surgery for rectal cancer.

BACKGROUND: Total mesorectal excision (TME) represents the "gold standard" of rectal cancer surgery. In locally advanced lesions neoadjuvant treatments (e.g. radiotherapy-nRT, radio chemotherapy-cnRT) have been shown to improve TME oncological results, reducing local recurrences rate. Nevertheless, these treatments have significant functional consequences impacting patients' quality of life (QoL). The resulting syndrome is known as Low Anterior Resection Syndrome (LARS). The purpose of this work was to evaluate the association between risk factors and the development of LARS in a prospective series of laparoscopic sphincter-saving TME. METHODS: The study was conducted as a retrospective observational epidemiological study of a prospective database, including all patients undergoing laparoscopic anterior resection surgery for rectal cancer at our Unit from 1st January 2013 to 31st May 2018. The diagnosis of LARS was performed using the LARS Score. We classified risk factors in patient-related, pre-, intra- and post-operative factors. RESULTS: The sample included 153 consecutive patients. Forty-one were affected by "low" rectal cancer, 74 by "middle" rectal cancer, 38 by "high" rectal cancer. The prevalence of overall LARS (major LARS + minor LARS) in our series was 35.9% (55/153 cases). Association between nRT and overall/major LARS was significant (respectively p = 0.03 and 0.02). Distal localization of tumor was also significantly associated with LARS [overall LARS (p = 0.03), major LARS (p = 0.014)]. CONCLUSIONS: In our study, neoadjuvant radiotherapy and tumor localization resulted independent risk factors for LARS after laparoscopic sphincter-saving TME. Tumor localization in the "middle" and "high" rectum resulted a protective factor compared to the localization in "low" rectum.

Oral neomycin and bacitracin are effective in preventing surgical site infections in elective colorectal surgery: a multicentre, randomized, parallel, single-blinded trial (COLORAL-1).

Several regimens of oral and intravenous antibiotics (OIVA) have been proposed with contradicting results, and the role of mechanical bowel preparation (MBP) is still controversial. This study aims to assess the effectiveness of oral antibiotic prophylaxis in preventing Surgical Site Infections (SSI) in elective colorectal surgery. In a multicentre trial, we randomized patients undergoing elective colorectal resection surgery, comparing the effectiveness of OIVA versus intravenous antibiotics (IVA) regimens to prevent SSI as the primary outcome (NCT04438655). In addition to intravenous Amoxicillin/Clavulanic, patients in the OIVA group received Oral Neomycin and Bacitracin 24 h before surgery. MBP was administered according to local habits which were not changed for the study. The trial was terminated during the COVID-19 pandemic, as many centers failed to participate as well as the pandemic changed the rules for engaging patients. Two-hundred and four patients were enrolled (100 in the OIVA and 104 in the IVA group); 3 SSIs (3.4%) were registered in the OIVA and 14 (14.4%) in the IVA group (p = 0.010). No difference was observed in terms of anastomotic leak. Multivariable analysis indicated that OIVA reduced the rate of SSI (OR 0.21 / 95% CI 0.06-0.78 / p = 0.019), while BMI is a risk factor of SSI (OR 1.15 / 95% CI 1.01-1.30 p = 0.039). Subgroup analysis indicated that 0/22 patients who underwent OIVA/MBP + vs 13/77 IVA/MBP- experienced an SSI (p = 0.037). The early termination of the study prevents any conclusion regarding the interpretation of the data. Nonetheless, Oral Neomycin/Bacitracin and intravenous beta-lactam/beta-lactamases inhibitors seem to reduce SSI after colorectal resections, although not affecting the anastomotic leak in this trial. The role of MBP requires more investigation.

Concurrent Chemoradiation in Anal Cancer Patients Delivered with Bone Marrow-Sparing IMRT: Final Results of a Prospective Phase II Trial.

We investigated the role of the selective avoidance of haematopoietically active pelvic bone marrow (BM), with a targeted intensity-modulated radiotherapy (IMRT) approach, to reduce acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. We designed a one-armed two-stage Simon's design study to test the hypothesis that BM-sparing IMRT would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05; ß = 0.20). A minimum of 21/39 (54%) with G0-G2 toxicity represented the threshold for the fulfilment of the criteria to define this approach as 'promising'. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. From December 2017 to October 2020, we enrolled 39 patients. Maximum observed acute HT comprised 20% rate of ≥G3 leukopenia and 11% rate of ≥G3 thrombocytopenia. Overall, 11 out of 39 treated patients (28%) experienced ≥G3 acute HT. Conversely, in 28 patients (72%) G0-G2 HT events were observed, above the threshold set. Hence, 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in this clinical setting.

FISSIT (Fistula Surgery in Italy) study: A retrospective survey on the surgical management of anal fistulas in Italy over the last 15 years.

BACKGROUND: Surgical treatment of anal fistulas is still a challenge. The aims of this study were to evaluate the adoption and healing rates for the different surgical techniques used in Italy over the past 15 years. METHODS: This was a multicenter retrospective observational study of patients affected by simple and complex anal fistulas of cryptoglandular origin who were surgically treated in the period 2003-2017. Surgical techniques were grouped as sphincter-cutting or sphincter-sparing and as technology-assisted or techno-free. All patients included in the study were followed for at least 12 months. RESULTS: A total of 9,536 patients (5,520 simple; 4,016 complex fistulas) entered the study. For simple fistulas, fistulotomy was the most frequently used procedure, although its adoption significantly decreased over the years (P < .0005), with an increase in sphincter-sparing approaches; the overall healing rate in simple fistulas was 81.1%, with a significant difference between sphincter-cutting (91.9%) and sphincter-sparing (65.1%) techniques (P = .001). For complex fistulas, the adoption of sphincter-cutting approaches decreased, while sphincter-sparing techniques were mildly preferred (P < .0005). Moreover, there was a significant trend toward the use of technology-assisted procedures. The overall healing rate for complex fistulas was 69.0%, with a measurable difference between sphincter-cutting (81.1%) and sphincter-sparing (61.4%; P = .001) techniques and between techno-free and technology-assisted techniques (72.5% and 55.0%, respectively; P = .001). CONCLUSION: Surgical treatment of anal fistulas has changed, with a trend toward the use of sphincter-sparing techniques. The overall cure rate has remained stable, even if the most innovative procedures have achieved a lower success rate.

Prospective, randomised, multicentre, open-label trial, designed to evaluate the best timing of closure of the temporary ileostomy (early versus late) in patients who underwent rectal cancer resection and with indication for adjuvant chemotherapy: the STOMAD (STOMa closure before or after ADjuvant therapy) randomised controlled trial.

INTRODUCTION: Temporary ileostomy is a valuable aid in reducing the severity of complications related to rectal cancer surgery. However, it is still unclear what is the best timing of its closure in relation to the feasibility of an adjuvant treatment, especially considering patient-reported outcomes and health system costs. The aim of the study is to compare the results of an early versus late closure strategy in patients with indication to adjuvant chemotherapy after resection for rectal cancer. METHODS AND ANALYSIS: This is a prospective multicentre randomised trial, sponsored by Rete Oncologica Piemonte e Valle d'Aosta (Oncology Network of Piedmont and Aosta Valley-Italy). Patients undergone to rectal cancer surgery with temporary ileostomy, aged >18 years, without evidence of anastomotic leak and with indication to adjuvant chemotherapy will be enrolled in 28 Network centres. An early closure strategy (between 30 and 40 days from rectal surgery) will be compared with a late one (after the end of adjuvant therapy). Primary endpoint will be the compliance to adjuvant chemotherapy with and without ileostomy. Complications associated with stoma closure as well as quality of life, costs and oncological outcomes will be assessed as secondary endpoints. ETHICS AND DISSEMINATION: The trial will engage the Network professional teams in a common effort to improve the treatment of rectal cancer by ensuring the best results in relation to the most correct use of resources. It will take into consideration both the patients' point of view (patient-reported outcome) and the health system perspective (costs analysis). The study has been approved by the Ethical Review Board of Città della Salute e della Scienza Hospital in Turin (Italy). The results of the study will be disseminated by the Network website, medical conferences and peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT04372992.

Tailoring the radiotherapy approach in patients with anal squamous cell carcinoma based on inguinal sentinel lymph node biopsy.

BACKGROUND AND OBJECTIVES: The aim of our study was to analyze the results of selective inguinal node irradiation in patients with anal cancer, based on the biopsy of the inguinal sentinel lymph node (SLN), in terms of local control and prognosis. METHODS: Records of patients with anal squamous cell carcinoma from January 2001 to December 2016 were retrospectively reviewed. Tc99 lymphoscintigraphy was performed in all the clinically inguinal negative patients, followed by radio-guided surgical removal of the inguinal SLN. All patients were treated with combined radiochemotherapy. In patients with negative sentinel nodes, the inguinal area was excluded in the radiotherapy field. RESULTS: A total of 123 patients, 76 females (61.8%), mean age 60.1 ± 12.19 years old, underwent intraoperative lymph node retrieval. The histological analysis showed metastasis in the SLN in 28 patients (22.8%). The mean follow-up was 43.44 ± 31.86 months. No inguinal recurrence was observed in patients with negative inguinal sentinel node(s). A statistically significant difference was observed for overall and disease-free survivals in a patient with positive and negative inguinal sentinel nodes. CONCLUSIONS: In patients with anal canal cancer, the exclusion of the inguinal regions from the radiotherapy field, in patients with negative SLN, does not compromise locoregional control nor prognosis.

Management of Hemorrhoidal Disease in Special Conditions: A Word of Caution.

BACKGROUND: Hemorrhoids are a common disease that is often considered an easy problem to solve. Unfortunately, some particular clinical conditions, including Inflammatory Bowel Diseases (IBD), pregnancy, immunosuppression, coagulopathy, cirrhosis with portal hypertension, and proctitis after radiotherapy, challenge hemorrhoids management and the outcomes. METHODS: Research and online contents related to hemorrhoids' treatment in special conditions are reviewed in order to help colorectal surgeons in daily practice. RESULTS: There are very limited data about the outcomes of hemorrhoids treatment in these subgroups of patients. Patients in pregnancy can be effectively treated with medical therapy, reserving surgical intervention in highly selected and urgent cases. In case of thrombosed haemorrhoids, the excision allows a fast symptoms' resolution, with a low incidence of recurrence and a long remission interval. In case of immunosuppressed patients, there is no consensus for the best treatment, even in most HIV positive patients, a surgical procedure can be safely proposed when indicated. There is no sufficient data in the literature related to transplanted patients. The surgical treatment of hemorrhoids in patients with IBD, especially Crohn's Disease, can be unsafe, although there is a paucity of literature on this topic. In case of previous pelvic radiotherapy, it must always be considered that severe complications, like abscesses and fistulas with subsequent pelvic and retroperitoneal sepsis, can occur after surgical treatment of hemorrhoids, so a conservative treatment is advocated. Moreover, caution is recommended in treating patients with coagulopathy, considering possible complications (mostly bleeding) also after outpatient treatments. In case of portal hypertension and cirrhosis, a 'conservative treatment' is recommended. Bleeding hemorrhoids can be treated with hemorrhoidectomy when they do not respond to other treatments. CONCLUSION: International literature is very scant about the treatment of patients affected by hemorrhoids in particular situations. A word of caution and concern even about the indication for minor outpatient procedures must be expressed in these patients, in order to avoid possible life-threatening complications. The first-line treatment is the conservative medical approach associated with the treatment of the primary disease.

Low Tenofovir Plasma Exposure in HIV Oral Pre-exposure Prophylaxis Recipients with Gastrointestinal Disorders.

Four pre-exposure prophylaxis (PrEP) users with gastro-intestinal disorders (sleeve gastrectomy, terminal ileitis, celiac disease or chronic diarrhea) and receiving oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) were included. Despite a self-reported high adherence, trough plasma tenofovir concentrations (after a supervised intake) were significantly lower than those observed in PrEP recipients without gastrointestinal disorders [21 (±9.1) vs. 138 (±85) ng/mL]. PrEP users with gastrointestinal disorders may need increased TDF doses or alternative prophylactic measures.

Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial.

PURPOSE: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with 18FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. METHODS: a one-armed two-stage Simon's design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the ß = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0-G2 acute HT to further proceed with the trial. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. RESULTS: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0-G2 events, way above the threshold set by the trial design. CONCLUSION: 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.

Proctitis: a glance beyond inflammatory bowel diseases.

Proctitis is an inflammation involving the anus and the distal part of the rectum, frequently diagnosed in the context of inflammatory bowel diseases (IBD). Nevertheless, when the standard therapy for IBD is ineffective, it becomes necessary for the clinician to review alternative etiologies, beginning from the broad chapter of infectious causes up to rare causes such as radiation, ischemia, diversion and traumatisms. While it is possible to find infectious proctitides caused by pathogens generally inducing extensive colitis, the growing incidence of both sexually transmitted infections and isolated proctitis reported in the recent years require a lot of attention. The risk appears to be higher in individuals participating in anal intercourse, especially men having sex with men (MSM) or subjects who use sex toys and participate to sex parties, dark rooms and so on. The commonest implicated pathogens are Neysseria gonorrhoeae, Chlamydia trachomatis, Herpes Simplex virus and Treponema pallidum. Herpes and Chlamydia infections mainly occur in HIV-positive MSM patients. Since symptoms and signs are common independently from etiology, performing a differential diagnosis based on clinical manifestations is complicated. Therefore, the diagnosis is supported by the combination of clinical history and physical examination and, secondly, by endoscopic, serologic and microbiologic findings. Particular emphasis should be given to simultaneous infections by multiple organisms. The involvement of experts in infectious diseases and in sexual health is crucial for the diagnostic and therapeutic management. The available therapies, empirically initiated or specific, in many cases are able to guarantee a good prognosis and to prevent relapses.

Intracorporeal or Extracorporeal Ileocolic Anastomosis After Laparoscopic Right Colectomy: A Double-blinded Randomized Controlled Trial.

OBJECTIVES: The aim of the study was to determine whether there are clinically relevant differences in outcomes between laparoscopic right colectomy (LRC) with intracorporeal ileocolic anastomosis (IIA) and LRC with extracorporeal IA (EIA). BACKGROUND: IIA and EIA are 2 well-established techniques for restoration of bowel continuity after LRC. There are no high-quality studies demonstrating the superiority of one anastomotic technique over the other. METHODS: This is a double-blinded randomized controlled trial comparing the outcomes of LRC with IIA and LRC with EIA in patients with a benign or malignant right-sided colon neoplasm. Primary endpoint was length of hospital stay (LOS). This trial was registered with ClinicalTrials.gov, number NCT03045107. RESULTS: A total of 140 patients were randomized and analyzed. Median operative time was comparable in IIA versus EIA group {130 [interquartile range (IQR) 105-195] vs 130 (IQR 110-180) min; P = 0.770} and no intraoperative complications occurred. The quicker recovery of bowel function after IIA than EIA [gas: 2 (IQR 2-3) vs 3 (IQR 2-3) days, P = 0.003; stool: 4 (IQR 3-5) vs 4.5 (IQR 3-5) days, P = 0.032] was not reflected in any advantage in the primary endpoint: median LOS was similar in the 2 groups [6 (IQR 5-7) vs 6 (IQR 5-8) days; P = 0.839]. No significant differences were observed in the number of lymph nodes harvested, length of skin incision, 30-day morbidity (17.1% vs 15.7%, P = 0.823), reoperation rate, and readmission rate between the 2 groups. CONCLUSIONS: LRC with IIA is associated with earlier recovery of postoperative bowel function than LRC with EIA; however, it does not reflect into a shorter LOS.

Immune inflammation indicators in anal cancer patients treated with concurrent chemoradiation: training and validation cohort with online calculator (ARC: Anal Cancer Response Classifier).

Background: In anal cancer, there are no markers nor other laboratory indexes that can predict prognosis and guide clinical practice for patients treated with concurrent chemoradiation. In this study, we retrospectively investigated the influence of immune inflammation indicators on treatment outcome of anal cancer patients undergoing concurrent chemoradiotherapy. Methods: All patients had a histologically proven diagnosis of squamous cell carcinoma of the anal canal/margin treated with chemoradiotherapy according to the Nigro's regimen. Impact on prognosis of pre-treatment systemic index of inflammation (SII) (platelet x neutrophil/lymphocyte), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were analyzed. Results: A total of 161 consecutive patients were available for the analysis. Response to treatment was the single most important factor for progression-free survival (PFS) and overall survival (OS). At univariate analysis, higher SII level was significantly correlated to lower PFS (p<0.01) and OS (p=0.046). NLR level was significantly correlated to PFS (p=0.05), but not to OS (p=0.06). PLR level significantly affected both PFS (p<0.01) and OS (p=0.02). On multivariate analysis pre-treatment, SII level was significantly correlated to PFS (p=0.0079), but not to OS (p=0.15). We developed and externally validated on a cohort of 147 patients a logistic nomogram using SII, nodal status and pre-treatment Hb levels. Results showed a good predictive ability with C-index of 0.74. An online available calculator has also been developed. Conclusion: The low cost and easy profile in terms of determination and reproducibility make SII a promising tool for prognostic assessment in this oncological setting.

Intraoperative air leak test reduces the rate of postoperative anastomotic leak: analysis of 777 laparoscopic left-sided colon resections.

BACKGROUND: The evidence supporting the use of the air leak test (ALT) after laparoscopic left-sided colon resection (LLCR) to test the colorectal anastomosis (CA) integrity aiming at reducing the rate of postoperative CA leakage (CAL) is not conclusive. The aim of this study was to challenge the use of ALT after elective LLCR. METHODS: It is a retrospective analysis of a prospectively collected database including all patients undergoing elective LLCR with primary CA and no proximal bowel diversion between January 1996 and June 2017. The decision to perform the ALT was based on the individual surgeon routine practice. A multivariate analysis was performed to identify independent risk factors for CAL. RESULTS: A total of 777 LLCR without proximal diversion were included in the analysis: the CA was tested in 398 patients (ALT group), while intraoperative ALT was not performed in 379 patients (No-ALT group). The two groups were similar in demographic characteristics, indication, and type of procedure. Intraoperative ALT was positive in 20 (5%) patients: a stoma was created in 14 (70%) patients, while 6 (30%) patients had a suture repair alone. Overall, postoperative CAL occurred in 32 patients (4.1%): the postoperative CAL rate was lower in ALT patients (2.5% vs. 5.8%, p = 0.025). A reoperation was needed in 87.5% of cases. No CAL occurred in the 20 patients with intraoperative positive ALT. Multivariate analysis showed that ASA score 3-4 (OR 5.39, 95% CI 2.53-11.51, p < 0.001) and male sex (OR 3.96, 95% CI 1.66-9.43, p = 0.002) were independent risk factors for postoperative CAL, while intraoperative ALT independently reduced the postoperative CAL rate (OR 0.40, 95% CI 0.18-0.88, p = 0.022). CONCLUSION: Intraoperative ALT allows to detect AL defects after LLCR that can be effectively managed intraoperatively, leading to a significant lower risk of postoperative CAL.

Comparing simultaneous integrated boost vs sequential boost in anal cancer patients: results of a retrospective observational study.

BACKGROUND: To evaluate clinical outcomes of simultaneous integrated boost (SIB) - intensity modulated radiotherapy (RT) in patients with non metastatic anal cancer compared to those of a set of patients treated with 3-dimensional conformal RT and sequential boost (SeqB). METHODS: A retrospective cohort of 190 anal cancer patients treated at 3 academic centers with concurrent chemo-RT employing either SIB or SeqB was analysed. The SIB-group consisted of 87 patients, treated with 2 cycles of Mitomycin (MMC) and 5-Fluorouracil (5FU) using SIB-IMRT delivering 42-45Gy/28-30 fractions to the elective pelvic lymph nodes and 50.4-54Gy/28-30fractions to the primary tumor and involved nodes, based on pre-treatment staging. The SeqB group comprised 103 patients, treated with MMC associated to either 5FU or Capecitabine concurrent to RT with 36 Gy/20 fractions to a single volume including gross tumor, clinical nodes and elective nodal volumes and a SeqB to primary tumor and involved nodes of 23.4 Gy/13 fractions. We compared colostomy-free survival (CFS), overall survival (OS) and the cumulative incidence of colostomy for each radiation modality. Cox proportional-hazards model addressed factors influencing OS and CFS. RESULTS: Median follow up was 34 (range 9-102) and 31 months (range 2-101) in the SIB and SeqB groups. The 1- and 2-year cumulative incidences of colostomy were 8.2% (95%CI:3.6-15.2) and 15.0% (95%CI:8.1-23.9) in the SIB group and 13.9% (95%CI: 7.8-21.8) and 18.1% (95%CI:10.8-27.0) in the SeqB group. Two-year CFS and OS were 78.1% (95%CI:67.0-85.8) and 87.5% (95%CI:77.3-93.3) in the SIB group and 73.5% (95%CI:62.6-81.7) and 85.4% (95%CI:75.5-91.6) in the SeqB, respectively. A Cox proportional hazards regression model highlighted an adjusted hazard ratio (AdjHR) of 1.18 (95%CI: 0.67-2.09;p = 0.560), although AdjHR for the first 24 months was 0.95 (95%CI: 0.49-1.84;p = 0.877) for the SIB approach. CONCLUSIONS: SIB-based RT provides similar clinical outcomes compared to SeqB-based in the treatment of patients affected with non metastatic anal cancer.

Preoperative stoma site marking: a simple practice to reduce stoma-related complications.

BACKGROUND: To evaluate the incidence and identify the risk factors of stoma-related complications in a consecutive series of patients treated at a single institution. METHODS: For this retrospective analysis, the medical records of patients followed up at the stoma care centre of our institution over the last 16 years were reviewed. The primary end point was the incidence of stoma-related complications. Risk factors were tested using univariate and multivariate Cox proportional hazards models. RESULTS: Of a total of 1076 patients, 604 received a colostomy and 472 an ileostomy. In all, 1055 stoma-related complications were recorded in 797 patients. Univariate analysis identified the following risk factors for stoma-related complications: male sex (p = 0.032), emergency surgery (p = 0.010), open surgery (p < 0.001), and ileostomy creation (p = 0.004). Preoperative stoma site marking was noted to play a protective role (hazard ratio 0.739; 95% confidence interval 0.576-0.947; p = 0.017). Multivariate analysis confirmed male sex and ileostomy creation as risk factors (p = 0.030 and p = 0.013, respectively) and preoperative stoma site marking as an independent protective factor (p = 0.001). CONCLUSIONS: Stoma-related complications are quite common, especially when an ileostomy is present. Preoperative stoma site marking was noted to play a highly protective role not only in reducing the complication rate but also in improving the patients' quality of life.

Dose to Pelvic Bone Marrow Defined with FDG-PET Predicts for Hematologic Nadirs in Anal Cancer Patients Treated with Concurrent Chemo-radiation.

PURPOSE: To investigate whether irradiated volume of pelvic active bone marrow (ACTBM) may predict decreased blood cells nadirs in anal cancer patients undergoing concurrent chemo-radiation. METHODS: Forty-four patients were analyzed and pelvic active bone marrow (ACTBM) was characterized employing 18FDG-PET. Dosimetric parameters on dose-volume histograms were correlated to nadirs with generalized linear modeling. RESULTS: ACTBM mean dose was significantly correlated to white blood cell (ß = -1.338; 95%CI: -2.455/-0.221; p = 0.020), absolute neutrophil count (ß = -1.651; 95%CI: -3.284/-0.183; p = 0.048), and platelets (ß = -0.031; 95%CI: -0.057/-0.004; p = 0.024) nadirs. Other dosimetric parameters were found to be correlated (ACTBM-V10,-V20,-V30and-V40). CONCLUSIONS: 18FDG-PET is able to define active bone marrow and may predict for decreased blood cells count nadirs.