Role of 0.4% glyceryl trinitrate ointment after haemorrhoidectomy: results of a prospective randomised study

INTRODUCTION: Conventional haemorrhoidectomy (CH) is well known to cause significant post-operative pain and delayed return to daily activities. Both surgical wounds and sphincterial apparatus spasms are likely responsible for the pain. In this study, we evaluated the role of glyceryl trinitrate ointment (GTN) in reducing post-operative pain, ameliorating wound healing and recovery after CH. PATIENTS AND METHODS: Between 01/08 and 12/11, 203 patients with symptomatic haemorrhoids were enrolled in the study and received (103 patients) or not (100 patients) 0.4 % GTN ointment for 6 weeks after surgery. Pain was assessed using a 10-cm linear visual analogue scale (VAS). Data on post-operative pain, wound secretion and bleeding, return to normal activities and complications were recorded. Data were analysed using Fisher's exact and Mann-Whitney tests. RESULTS: GTN-treated group experienced significantly less pain during the first week after surgery (p < 0.0001). This difference was more evident starting from post-operative day 4 (p < 0.0001). A significant higher percentage of untreated patients experienced severe pain (mean VAS score > 7) (10 % vs 31 %). There were significant differences in terms of secretion time (p = 0.0052) and bleeding time (p = 0.02) in favor of GTN. In addition, the duration of itching was less in the GTN group (p = 0.0145). Patients treated with GTN were able to an early return to daily activities compared to untreated (p < 0.0001). Fifteen GTN-treated patients (14.6 %) discontinued the application because of local discomfort and headache. CONCLUSIONS: GTN ointment enhances significantly post-operative recovery, reducing pain in terms of duration and intensity. This effect might be secondary to a faster wound healing expressed by reduced secretion, bleeding and itching time

Prevalence of Defaecatory Disorders in Morbidly Obese Patients Before and After Bariatric Surgery

BACKGROUND: The prevalence of obesity is increasing worldwide and has lately reached epidemic proportions in western countries. Several epidemiological studies have consistently shown that both overweight and obesity are important risk factors for the development of various functional defaecatory disorders (DDs), including faecal incontinence and constipation. However, data on their prevalence as well as effectiveness of bariatric surgery on their correction are scant. The primary objective of this study was to estimate the effect of morbid obesity on DDs in a cohort of patients listed for bariatric surgery. We also evaluated preliminary results of the effects of sleeve gastrectomy on these disorders. PATIENTS AND METHODS: A questionnaire-based study was proposed to morbidly obese patients having bariatric surgery. Data included demographics, past medical, surgical and obstetrics histories, as well as obesity related co-morbidities. Wexner Constipation Score (WCS) and the Faecal Incontinence Severity Index (FISI) questionnaires were used to evaluate constipation and incontinence. For the purpose of this study, we considered clinically relevant a WCS ≥5 and a FISI score ≥10. The same questionnaires were completed at 3 and 6 months follow-up after surgery. RESULTS: A total of 139 patients accepted the study and 68 underwent sleeve gastrectomy and fully satisfied our inclusion criteria with a minimum follow-up of 6 months. Overall, mean body mass index (BMI) at listing was 47 ± 7 kg/m(2) (range 35-67 kg/m(2)). Mean WCS was 4.1 ± 4 (range 0-17), while mean FISI score (expressed as mean±standard deviation) was 9.5 ± 9 (range 0-38). Overall, 58.9% of the patients reported DDs according to the above-mentioned scores. Twenty-eight patients (20%) had WCS ≥5. Thirty-five patients (25%) had a FISI ≥10 while 19 patients (13.7%) reported combined abnormal scores. Overall, DDs were more evident with the increase of obesity grade: Mean BMI decreased significantly from 47 ± 7 to 36 ± 6 and to 29 ± 4 kg/m(2) respectively at 3 and 6 months after surgery (p < 0.0001). According to the BMI decrease, the mean WCS decreased from 3.7 ± 3 to 3.1 ± 4 and to 1.6 ± 3 respectively at 3 and 6 months (p = 0.02). Similarly, the FISI score decreased from 10 ± 8 to 3 ± 4 and to 1 ± 2 respectively at 3 and 6 months (p = 0.0001). CONCLUSIONS: Defaecatory disorders are common in morbidly obese patients. The risk of DDs increases with BMI. Bariatric surgery reduces DDs, mainly faecal incontinence, and these findings correlated with BMI reduction

3D pelvimetry and biometric measurements: a surgical perspective for colorectal resections

Purpose: Male sex, high BMI, narrow pelvis, and bulky mesorectum were acknowledged as clinical variables correlated with a difficult pelvic dissection in colorectal surgery. This paper aimed at comparing pelvic biometric measurements in female and male patients and at providing a perspective on how pelvimetry segmentation may help in visualizing mesorectal distribution. Methods: A 3D software was used for segmentation of DICOM data of consecutive patients aged 60&nbsp;years, who underwent elective abdominal CT scan. The following measurements were estimated: pelvic inlet, outlet, and depth; pubic tubercle height; distances from the promontory to the coccyx and to S3/S4; distance from S3/S4 to coccyx\u2019s tip; ischial spines distance; pelvic tilt; offset angle; pelvic inlet angle; angle between the inlet/sacral promontory/coccyx; angle between the promontory/coccyx/pelvic outlet; S3 angle; and pelvic inlet to pelvic depth ratio. The measurements were compared in males and females using statistical analyses. Results: Two-hundred patients (M/F 1:1) were analyzed. Out of 21 pelvimetry measurements, 19 of them documented a significant mean difference between groups. Specifically, female patients had a significantly wider pelvic inlet and outlet but a shorter pelvic depth, and promontory/sacral/coccyx distances, resulting in an augmented inlet/depth ratio when comparing with males (p &lt; 0.0001). The sole exceptions were the straight conjugate (p = 0.06) and S3 angle (p = 0.17). 3D segmentation provided a perspective of the mesorectum distribution according to the pelvic shape. Conclusion: Significant differences in the structure of pelvis exist in males and females. Surgeons must be aware of the pelvic shape when approaching the rectum

Study protocol for the OligoMetastatic Esophagogastric Cancer (OMEC) project: A multidisciplinary European consensus project on the definition and treatment for oligometastatic esophagogastric cancer

Background: A uniform definition and treatment for oligometastatic esophagogastric cancer is currently lacking. However, a comprehensive definition of oligometastatic esophagogastric cancer is necessary to initiate studies on local treatment strategies (e.g. metastasectomy or stereotactic radiotherapy) and new systemic therapy agents in this group of patients. For this purpose, the OligoMetastatic Esophagogastric Cancer (OMEC) project was established. The OMEC-project aims to develop a multidisciplinary European consensus statement on the definition, diagnosis, and treatment for oligometastatic esophagogastric cancer and provide a framework for prospective studies to improve outcomes of these patients. Methods: The OMEC-project consists of five studies, including 1) a systematic review on definitions and outcomes of oligometastatic esophagogastric cancer; 2) real-life clinical scenario discussions in multidisciplinary expert teams to determine the variation in the definition and treatment strategies; 3) Delphi consensus process through a starting meeting, two Delphi questionnaire rounds, and a consensus meeting; 4) publication of a multidisciplinary European consensus statement; and 5) a prospective clinical trial in patients with oligometastatic esophagogastric cancer. Discussion: The OMEC project aims to establish a multidisciplinary European consensus statement for oligometastatic esophagogastric cancer and aims to initiate a prospective clinical trial to improve outcomes for these patients. Recommendations from OMEC can be used to update the relevant guidelines on treatment for patients with (oligometastatic) esophagogastric cancer

Clinical outcomes of patients with complicated post-operative course after gastrectomy for cancer: a GIRCG study using the GASTRODATA registry

Gastrectomy for gastric cancer is still performed in Western countries with high morbidity and mortality. Post-operative complications are frequent, and effective diagnosis and treatment of complications is crucial to lower the mortality rates. In 2015, a project was launched by the EGCA with the aim of building an agreement on list and definitions of post-operative complications specific for gastrectomy. In 2018, the platform www.gastrodata.org was launched for collecting cases by utilizing this new complication list. In the present paper, the Italian Research Group for Gastric Cancer endorsed a collection of complicated cases in the period 2015–2019, with the aim of investigating the clinical pictures, diagnostic modalities, and treatment approaches, as well as outcome measures of patients experiencing almost one post-operative complication. Fifteen centers across Italy provided 386 cases with a total of 538 complications (mean 1.4 complication/patient). The most frequent complications were non-surgical infections (gastrointestinal, pulmonary, and urinary) and anastomotic leaks, accounting for 29.2% and 17.3% of complicated patients, with a median Clavien–Dindo score of II and IIIB, respectively. Overall mortality of this series was 12.4%, while mortality of patients with anastomotic leak was 25.4%. The clinical presentation with systemic septic signs, the timing of diagnosis, and the hospital volume were the most relevant factors influencing outcome

Detection of Emerging and Re-Emerging Pathogens in Surface Waters Close to an Urban Area

Current knowledge about the spread of pathogens in aquatic environments is scarce probably because bacteria, viruses, algae and their toxins tend to occur at low concentrations in water, making them very difficult to measure directly. The purpose of this study was the development and validation of tools to detect pathogens in freshwater systems close to an urban area. In order to evaluate anthropogenic impacts on water microbiological quality, a phylogenetic microarray was developed in the context of the EU project µAQUA to detect simultaneously numerous pathogens and applied to samples from two different locations close to an urban area located upstream and downstream of Rome in the Tiber River. Furthermore, human enteric viruses were also detected. Fifty liters of water were collected and concentrated using a hollow-fiber ultrafiltration approach. The resultant concentrate was further size-fractionated through a series of decreasing pore size filters. RNA was extracted from pooled filters and hybridized to the newly designed microarray to detect pathogenic bacteria, protozoa and toxic cyanobacteria. Diatoms as indicators of the water quality status, were also included in the microarray to evaluate water quality. The microarray results gave positive signals for bacteria, diatoms, cyanobacteria and protozoa. Cross validation of the microarray was performed using standard microbiological methods for the bacteria. The presence of oral-fecal transmitted human enteric-viruses were detected using q-PCR. Significant concentrations of Salmonella, Clostridium, Campylobacter and Staphylococcus as well as Hepatitis E Virus (HEV), noroviruses GI (NoGGI) and GII (NoGII) and human adenovirus 41 (ADV 41) were found in the Mezzocammino site, whereas lower concentrations of other bacteria and only the ADV41 virus was recovered at the Castel Giubileo site. This study revealed that the pollution level in the Tiber River was considerably higher downstream rather than upstream of Rome and the downstream location was contaminated by emerging and re-emerging pathogens

Definition, diagnosis and treatment of oligometastatic oesophagogastric cancer: A Delphi consensus study in Europe

BACKGROUND Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. METHODS In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%). RESULTS A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). CONCLUSION The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials

European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4)

INTRODUCTION: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). METHODS: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. RESULTS: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. $^{18}$F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended. DISCUSSION: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment

European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4)

Introduction: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). Methods: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. Results: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI &gt; 2 years, upfront local treatment is additionally recommended. Discussion: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment

Development of Mathematical Models for the Analysis of Hepatitis Delta Virus Viral Dynamics

BACKGROUND: Mathematical models have shown to be extremely helpful in understanding the dynamics of different virus diseases, including hepatitis B. Hepatitis D virus (HDV) is a satellite virus of the hepatitis B virus (HBV). In the liver, production of new HDV virions depends on the presence of HBV. There are two ways in which HDV can occur in an individual: co-infection and super-infection. Co-infection occurs when an individual is simultaneously infected by HBV and HDV, while super-infection occurs in persons with an existing chronic HBV infection. METHODOLOGY/PRINCIPAL FINDINGS: In this work a mathematical model based on differential equations is proposed for the viral dynamics of the hepatitis D virus (HDV) across different scenarios. This model takes into consideration the knowledge of the biology of the virus and its interaction with the host. In this work we will present the results of a simulation study where two scenarios were considered, co-infection and super-infection, together with different antiviral therapies. Although, in general the predicted course of HDV infection is similar to that observed for HBV, we observe a faster increase in the number of HBV infected cells and viral load. In most tested scenarios, the number of HDV infected cells and viral load values remain below corresponding predicted values for HBV. CONCLUSIONS/SIGNIFICANCE: The simulation study shows that, under the most commonly used and generally accepted therapy approaches for HDV infection, such as lamivudine (LMV) or ribavirine, peggylated alpha-interferon (IFN) or a combination of both, LMV monotherapy and combination therapy of LMV and IFN were predicted to more effectively reduce the HBV and HDV viral loads in the case of super-infection scenarios when compared with the co-infection. In contrast, IFN monotherapy was found to reduce the HDV viral load more efficiently in the case of super-infection while the effect on the HBV viral load was more pronounced during co-infection. The results suggest that there is a need for development of high efficacy therapeutic approaches towards the specific inhibition of HDV replication. These approaches may additionally be directed to the reduction of the half-life of infected cells and life-span of newly produced circulating virions