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.

Efficacy and safety of Propionibacterium extract gel versus glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized controlled trial.

AIM: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF. METHOD: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis. RESULTS: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes. CONCLUSION: While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events.

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.

Deadlock of proctologic practice in Italy during COVID-19 pandemic: a national report from ProctoLock2020.

Proctology is one of the surgical specialties that suffered the most during COVID-19 pandemic. Using data from a cross-sectional worldwide web survey, we aimed to snapshot the current status of proctologic practice in Italy with differences between three macro areas (North, Centre, South). Specialists affiliated to renowned scientific societies with an interest in coloproctology were invited to join a 27-item survey. Predictive power of respondents' and hospitals' demographics on the change of status of surgical activities was calculated. The study was registered at ClinicalTrials.gov (NCT04392245). Of 299 respondents from Italy, 94 (40%) practiced in the North, 60 (25%) in the Centrer and 82 (35%) in the South and Islands. The majority were men (79%), at consultant level (70%), with a mean age of 46.5 years, practicing in academic hospitals (39%), where a dedicated proctologist was readily available (68%). Southern respondents were more at risk of infection compared to those from the Center (OR, 3.30; 95%CI 1.46; 7.47, P = 0.004), as were males (OR, 2.64; 95%CI 1.09; 6.37, P = 0.031) and those who routinely tested patients prior to surgery (OR, 3.02; 95%CI 1.39; 6.53, P = 0.005). The likelihood of ongoing surgical practice was higher in the South (OR 1.36, 95%CI 0.75; 2.46, P = 0.304) and in centers that were not fully dedicated to COVID-19 care (OR 4.00, 95%CI 1.88; 8.50, P < 0.001). The results of this survey highlight important factors contributing to the deadlock of proctologic practice in Italy and may inform the development of future management strategies.

Screening for Squamous Cell Anal Cancer in HIV Positive Patients: A Five-Year Experience.

AIM: Potential screening modalities for early diagnosis of squamous cell anal cancer (SCC) in HIV patients include digital anorectal examination (DARE), anal Papanicolaou testing (Pap test), human papilloma virus (HPV) co-testing, and high-resolution anoscopy. The aim of this study was to demonstrate the results of a five-year screening program for SCC in HIV patients. MATERIALS AND METHODS: We conducted a retrospective study on 204 HIV patients who underwent a screening program for SCC from October 2010 to January 2015. All patients were screened by DARE, anal Pap test, including HPV test and cytology, and high-resolution video-proctoscopy (HR-VPS) with and without acetic acid 3%. Depending on macroscopic appearance and biopsies, patients underwent observation or treatment. Median follow-up was 36 months. RESULTS: Cytologic abnormalities (Cyt+) for high-risk HPV genotypes were recorded in 34% of patients. HR-VPS was positive in 59 patients (29%), of whom 13 patients (22%) were positive for warts; the rest have typical features of anal intraepithelial neoplasia (AIN). Sixteen (8%) patients had AIN (AIN I-III) and underwent wide local excision, ablation, or imiquimod. Absence of progression was recorded. Fourteen patients (7%) had SCC: eight (57%) with no evidence of recurrence, two (14%) had recurrence, and four (29%) died from metastatic disease. CONCLUSIONS: Our data demonstrated a successful screening program in preventing SCC in HIV patients. We demonstrate the advantages of progression towards SCC. Moreover, we used a new screening tool, the HR-VPS, a low-cost and manageable instrument to collect patients' long-term data.

Indications for the laparoscopic approach to acute small bowel obstruction: A retrospective review of 50 cases, a literature review, and a single hospital's preliminary experience.

Small bowel obstruction (SBO) is mainly caused by postoperative adhesions, but a broad spectrum of diseases may cause this pathogenetic condition. Laparoscopic treatment represents an efficient approach to SBO. The aim of this paper was to review a single center's experience with a minimally invasive approach to multiple pathologic scenarios causing SBO. From January 2010 to December 2012, 50 consecutive patients underwent laparoscopic surgery for mechanical SBO. In 90% of patients, the surgical procedure was totally laparoscopic, while 10% required conversion to midline laparotomy. In-hospital morbidity was 15% among totally laparoscopic patients and 40% among those who underwent conversion to midline laparotomy. Thirty-day mortality was zero. One patient died 4 months postoperatively from neoplastic disease progression; the remaining patients were free from occlusive symptoms at follow-up. The minimally invasive technique applies to a broad spectrum of cases. A larger cohort of patients seems necessary to reproduce our results and confirm the effectiveness of a laparoscopic approach to SBO.

Preliminary results of prophylactic HIPEC in patients with locally advanced gastric cancer.

BACKGROUND: The prognosis of locally advanced Gastric Cancer following surgical therapy alone is poor. Peritoneum represents a preferential site of dissemination in such neoplasm. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used in association with cytoreductive surgery (CRS) in the treatment of GC peritoneal carcinomatosis (PC). Aim of our preliminary experience is reporting our data on prophylactic HIPEC (P-HIPEC) in patients with GC at high risk of developing PC. METHODS: Eleven patients underwent P-HIPEC at our General and Emergency Surgery Department. All the patients were affected of high risk GC: serosa invasive tumors (T4), conventional cytology-positive or quantitative PCR detection of CEA mRNA on peritoneal lavage. Seven subtotal and four total gastrectomies with D2 or D2+ were performed. All the anastomoses were made before HIPEC. The procedure was carried out for 60 minutes with Mytomicin C and Cisplatin in all patients. Post-operative monitoring in Intensive Care Unit least for 24-48 hours. Oral nutrition was started precociously (day 5) also according with bowel movements and stool/gas passage. Follow-up took place in all patients at 1 month from surgery then every 6 months for 2 years and every 12 months for the following years. RESULTS: In four patients a neoadjuvant treatment was scheduled due to T or N stage at pre-operative evaluation. Gastric resection was guided on tumor location while the choice of performing a D2 or D2 + lymphadenectomy was up to preoperative imaging and intra-operative nodal status. No intra-operative complications were recorded. Median operation time was 398 minutes. In our series we recorded 20 adverse events. Median number for each patient was 1 adverse effect (range 0-2). Eight patients experienced a surgical adverse effect (G2-G3) that did not require any surgical treatment. Only one patient with duodenal stump dehiscence and intra-abdominal sepsis (G4-G5) underwent re-operation and died for severe hemorrhagic pancreatitis. Another patient died for ARDS. Per-operative mortality was 18%. Both patients were older then 70 years old. Median hospital stay was 14 days. Median follow-up was 15.9 months. Median survival was 29.6 months and median DFS was 20 months. Only one patient developed a peritoneal recurrence at 12 months and died for disease progression. Seven patients are still alive and disease free at last follow-up. One patient affected of variable immunodeficiency died at 9 months for pulmonary sepsis without any sign of local recurrence. CONCLUSIONS: Peritoneal dissemination appears to be a strong determinant in defining GC patients prognosis. Even after curative resection, peritoneal recurrence develops in about 60% of the patients with T3 and T4 tumors, and up to 40% of resected gastric cancer patients die as a direct result of peritoneal dissemination. Clinical trials showed that surgery plus HIPEC was associated with a significant improvement in survival compared to surgery alone in patients affected of GC with resectable PC. At present day there are not studies evaluating the role of P-HIPEC in patients at high risk of developing PC. The rationale of P-HIPEC is based on the concept that positive peritoneal lavage is considered an M1 (stage IV) similarly to macroscopic PC by the 7th TNM classification. Also analogous is the median survival of this 2 groups of patients. Detection of peritoneal micrometastases with cytologic examination has been considered a major method to predict peritoneal recurrences; the sensitivity of this assay is low. Recently, molecular approaches using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) technique has made possible the increase in the sensitivity. We can conclude, although the preliminary experience, that prophylactic HIPEC in locally advanced gastric cancer is feasible, increasing median survival compared to surgery alone. For sure this procedure need to be performed in the highly specialized centres strongly respecting the eligibility criteria.

Epigenetic modulation by methionine deficiency attenuates the potential for gastric cancer cell dissemination.

INTRODUCTION: Methionine dependency occurs frequently in tumor cells. Here we have investigated the effect of methionine deficiency on metastatic potential of gastric cancer cells in vitro and in vivo. MATERIALS AND METHODS: Model of peritoneal carcinomatosis and xenograft was generated by intraperitoneal or subcutaneous implantation of gastric cancer cells in NOD-SCID mice. In comparison to control medium, 3-day culture of MKN45, MKN74, and KATOIII cells in a methionine-deficient medium inhibited cell proliferation, increased the rate of cell apoptosis, and reduced cell adhesion and migration. In the xenograft model induced by implantation of MNK45 and MNK74 cells, two cycles of methionine-deficient diet reduced the tumor growth. Further on, a 10-day cycle of methionine-deficient diet reduced the number of peritoneal nodules in the model of peritoneal carcinomatosis induced by MKN45 cells injection. Finally, a microarray analysis of the methylation of promoter CpG islets demonstrated that methionine deficiency reduced the promoter methylation of E-cadherin whose expression was markedly increased in vivo and in vitro. RESULTS: In summary, we have provided evidence that a methionine-deficient diet modulates the growth of gastric tumor cells and in vitro deficiency of methionine increased apoptosis and decreased cellular adhesion and migration associated to epigenetic change of E-cadherin gene, in vivo and in vitro.

Gene expression changes induced by HIPEC in a murine model of gastric cancer.

BACKGROUND: Peritoneal carcinogenesis (PC) is the most frequent pattern of metastasis in patients with locally advanced gastric cancer. Despite this, there is a consensus on the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of PC from gastric cancer. The molecular mechanisms involved in beneficial effects of HIPEC remain unexplored. MATERIALS AND METHODS: Human gastric cancer MKN45 cells were injected into the peritoneal cavity of immune-deficient NOD-SCID mice. After induction of PC, the animals were randomized into five groups: HIPEC with mitomycin and cisplatin; normothermic intraperitoneal chemotherapy (NIPEC); normothermic intraperitoneal saline; hyperthermic intraperitoneal saline alone; no treatment. After 10 days of treatment, the mice were sacrificed and the extent of PC was assessed. RESULTS: Compared with the other groups of treatment, HIPEC reduced the extent and severity of peritoneal dissemination as measured by assessing the total number of peritoneal and mesenteric nodules (p<0,05) and the HIPEC procedure increased median survival significantly. By gene array analysis, HIPEC was found to effectively modulate the expression of a subset of genes involved in formation of peritoneal metastasis, including adenomatous polyposis coli; beta (3) subunit of the integrin gene; chemokine stromal cell-derived factor-1 receptor; spleen tyrosine kinase; vascular endothelial growth factor receptor 3; collagen, type IV, alpha 2 and Carbossi-terminal binding proteins 1. CONCLUSION: In the present study we have provided evidence that HIPEC protects against peritoneal dissemination in a mouse model of peritoneal gastric carcinogenesis and brings about specific changes in gene expression wich may be related to this protection.

Role of FDG-PET/CT in follow-up of patients treated with resective gastric surgery for tumour.

INTRODUCTION: Gastric cancer has a poor prognosis and a high rate of recurrences after surgery. The optimal method for assessing early recurrences is not defined: conventional imaging (ultrasonography, CT and MRI) have difficulty in detecting them, because they don't give information regarding metabolic features or tumor response to chemotherapy. Actually 18F-fluorodeoxyglucose positron emission (18FDG-PET) has several indications for the primary staging and the follow-up of colon-rectal, lung, breast, neck cancers and lymphoma, but its clinical role in gastric cancer is not assessed. Our study analyzes the role of 18FDG-PET integrated with CT scan in the detection of gastric cancer recurrence. MATERIALS AND METHODS: We retrospectively reviewed 50 patients which underwent follow-up 18FDG-PET/CT from 2006 to 2009 after radical surgery for gastric adenocarcinoma. Each study was repeated every 6 months for the first two years after surgery and every 12 months for the subsequent three years. RESULTS: 18FDG-PET/CT was positive for suspected neoplastic disease in 29 (58%) and negative in 21 (42%) patients, with 3 false positive and 3 false negative results. 18FDG-PET/CT showed highly effectiveness in early detection of recurrences, as observed in 17 patients that were totally asymptomatic, allowing the initiation of multimodal treatment resulting in an important increasing of survival. CONCLUSIONS: 18FDG-PET-CT has a very good sensitivity (89.7%) and specificity (85.7%) in detecting local and distant recurrences during post-operative follow-up. Positive 18FDG-PET/CT findings may lead to an early change in the management of these patients, directing them towards rescue surgery or chemotherapy thereby improving their overall survival

[Preliminary experience on the application of metallic stents for treatment of colorectal malignant stenosis]. / Esperienza preliminare nell'applicazione degli stent metallici autoespandibili per il trattamento delle stenosi maligne colo-rettali.

OBJECTIVE: Application of SEMS in treating colorectal obstruction caused by both intrinsic and extrinsic tumours. METHODS: From December 2007 to February 2008 two patient underwent colorectal stenting. The first patient was affected by sigma neoplasia with multiple lung and liver metastases; the second one had a distal colonic obstruction caused by pelvic relapse of endometrial adenocarcinoma. RESULTS: In both patients successful decompression, defined as complete relief of bowel obstruction as judged by clinical symptoms and radiographic observation, was achieved. The first patient died 1 month later for disease progression after the I cycle with Capecitabine. The second patient is undergoing the II cycle with Adriamicina and Cisplatino. DISCUSSION: In our experience no precocious or posthumous complications were observed and we evaluated that SEMSs are useful in both intrinsic and extrinsic colorectal malignancies. CONCLUSIONS: SEMSs allow a rapid decompression, reduce the number of emergency surgical procedures--and also the need for stomas--in poor general condition patients, achieving a better quality of life for patient with a short estimated life and a one-stage elective surgery for patient with resectable disease.