Destiny for Rendezvous: Is Cholecysto/Choledocholithiasis Better Treated with Dual- or Single-Step Procedures?

Biliary lithiasis is common worldwide, affecting almost 20% of the general population, though few experience symptoms. The frequency of choledocholithiasis in patients with symptomatic cholelithiasis is estimated to be 10-33%, depending on patients' age. Unlike gallbladder lithiasis, the medical and surgical treatment of common bile duct stones is uncertain, having changed over the last few years. The prior gold standard treatment for cholelithiasis and choledocholithiasis was open cholecystectomy with bile duct clearance, choledochotomy, and/or surgical sphincterotomy. In the last 10-15 years, new treatment approaches to the complex pathology of choledocholithiasis have emerged with the advent of endoscopic retrograde cholangiopancreatography (ERCP), laparoscopic surgery, and advanced diagnostic procedures. Although ERCP followed by laparoscopic cholecystectomy is the preferred mode of management, a single-step strategy (laparo-endoscopic rendezvous) has gained acceptance due to lesser morbidity and a lower risk of iatrogenic damage. Given the above, a tailored approach relying on careful evaluation of the disease is necessary in order to minimize complication risks and overall costs. Yet, the debate remains open, with no consensus on the superiority of laparo-endoscopic rendezvous to more conventional approaches.

Swab test in biological fluids as predictor of COVID-19 transmission risk during surgery: a prospective cross-sectional study from an Italian COVID center.

BACKGROUND: The contamination of body fluids by Severe Acute Respiratory Syndrome Coronavirus 2 during surgery is current matter of debate in the scientific literature concerning CoronaVIrus Disease 2019. Surgical guidelines were published during the first wave of the COVID-19 pandemic and recommended to avoid laparoscopic surgery as much as possible, in fear that the chimney effect of high flow intraperitoneal gas escape during, and after, the procedure would increase the risk of viral transmission. AIM: The aim of this study was to evaluate the possibility of SARS-CoV-2 transmission during surgery by searching for viral RNA in serial samplings of biological liquids. METHODS: This is a single center prospective cross-sectional study. We used a real-time reverse transcriptase (RT) polymerase chain reaction (PCR) test to perform swab tests for the qualitative detection of nucleic acid from SARS-CoV-2 in abdominal fluids, during emergency surgery and on the first post-operative day. In the case of thoracic surgery, we performed a swab test of pleural fluids during chest drainage placement as well as on the first post-operative day. RESULTS: A total of 20 samples were obtained: 5 from pleural fluids, 13 from peritoneal fluids and two from biliary fluid. All 20 swabs performed from biological fluids resulted negative for SARS-CoV-2 RNA detection. CONCLUSION: To date, there is no scientific evidence of possible contagion by laparoscopic aerosolization of SARS-CoV-2, neither is certain whether the virus is effectively present in biological fluids.

Colonic Perforation as Initial Presentation of Amyloid Disease: Case Report and Literature Review.

INTRODUCTION: Amyloidosis is an uncommon disease caused by the deposition of amyloid fibrils in tissues. This disease does not usually require surgical intervention, which could be warranted in the presence of complications such as bleeding, obstruction, or perforation. We present a case of primary amyloidosis of the colon in a patient affected by polymyositis who underwent Hartmann's procedure after a spontaneous colonic perforation. After 2 months of well-being, the patient underwent two consecutive surgical procedures for stenosis of the ostomy orifice. AREAS COVERED: A review of the literature has been performed, gathering case reports highlighting the distribution of this disease by age, gender, location, and treatment when available. EXPERT COMMENTARY: Gastrointestinal amyloid disease is a rare condition, and it could be considered among the rare causes of intestinal perforation. Timely surgical management is often necessary.

Early versus delayed approach in cholecystectomy after admission to an emergency department. A multicenter retrospective study.

BACKGROUND: Discussion regarding the timing of cholecystectomy for acute cholecystitis is still ongoing. This study evaluates the outcomes of patients who underwent surgery for acute cholecystitis after emergency admission at St. Orsola University Hospital of Bologna and Umberto I Hospital La Sapienza University of Rome. PATIENTS AND METHODS: . We performed a retrospective study on 464 patients who underwent cholecystectomy for acute cholecystitis. We divided patients in three groups based on the time elapsed between the onset of symptoms and surgery: within 72 hours (Group A), between 72 hours and 6 weeks (Group B) and after 6 weeks (Group C). We performed both univariate and multivariate statistical analysis on the data collected. RESULTS: The best results were in Group C, with significant differences with the others two groups: higher rates of laparoscopic technique (93% of cases), no mortality, better morbidity and shorter hospital stay. On the contrary, no significant differences were observed between Groups A and B: laparoscopic cholecystectomy 67% vs 66%, morbidity (Clavien-Dindo III-IV) 5% vs 5%, mortality 2% vs 1%, hospital stay 6,6 vs 5,6 days. Conversion rate was 11% in Group A, 18% in Group B and 4% in Group C. CONCLUSION: Our experience shows better results for cholecystectomies performed after 6 weeks from the onset of symptoms, while earlier cholecystectomies have worse outcomes regardless if they are performed before or after 72 hours from the onset of symptoms.

Breast cancer screening in women taking hormone replacement therapy needs updating.

Breast cancer screening by mammography is widely used. The diagnostic accuracy is limited, with a positive predictive value of 16%. Therefore, a stepwise investigation, with repeat mammography and confirmation by pathology, is usually proposed. Although this stepwise investigation intends to avoid overtreatment, the many false positives result in unnecessary fear and diagnostic surgery in many women. The false negatives are not known since these women have not been investigated. Given the estimated low risk of missing breast cancer and the slow growth, repeating a screening mammography every two years is sufficient. The false positive screening results, increase with breast density, and breast density increases when hormone replacement therapy (HRT) is given. It, therefore, is suggested to use clinical judgment and stop HRT for 3 to 6 months before repeating the mammography instead of starting immediately a stepwise investigation in all women.

The importance of rotation to teach secure half-hitch sequences in surgery.

Background: Knot security of half-knot (H) sequences varies with rotation, but half-knots risk destabilisation. Objectives: To investigate the rotation of half-hitch (S) sequences on knot security. Materials and Methods: The loop and knot security of symmetrical and asymmetrical sliding and blocking half-hitch sequences was measured using a tensiometer. Results: Loop security of symmetrical sliding half-hitch sequences is much higher than asymmetrical sequences, increasing from 6+2 to 21+2 and from 27+6 to 48+5 Newton (N) for 2 and 4 half-hitches respectively (both P<0.0001). Symmetrical sliding sequences are more compact and remain in the same plane, squeezing the passive thread, while asymmetrical sequences rotate loosely around the passive end. Blocking sequences are superior when asymmetrical since changing the passive end acts like changing rotation, transforming the asymmetrical sliding into a symmetrical blocking half-hitch on the new passive thread. The knot security of 2 sliding and 1 blocking half-hitch doubles from 52+3 to 98+2 N for the worst (asymmetric sliding and symmetric blocking, SSaSsb) or best rotation sequences (SSsSab). Adding a second asymmetric blocking half-hitch (Sab) increases security further to 105+3 N. The overall knot security of four-throw, correctly rotated, half-hitch (SSsSabSab) or half-knot (H2H1sH1s, H2H2a and H2H2s) sequences is similar for four suture diameters. Conclusion: Rotation affects the security of half-hitch sequences, which should be symmetrical when sliding, and asymmetrical when blocking. What is new?: Half-hitch sequences are clinically superior to half-knot sequences. They do not risk destabilisation, and loop security improves approximation of tissues under traction, permitting tight knots.

A proof of concept that experience-based management of endometriosis can complement evidence-based guidelines.

Background: Management of endometriosis should be based on the best available evidence. The pyramid of evidence reflects unbiased observations analysed with traditional statistics. Evidence-based medicine (EBM) is the clinical interpretation of these data by experts. Unfortunately, traditional statistical inference can refute but cannot confirm a hypothesis and clinical experience is considered a personal opinion. Objectives: A proof of concept to document clinical experience by considering each diagnosis and treatment as an experiment with an outcome, which is used to update subsequent management. Materials and Methods: Experience and knowledge-based questions were answered on a 0 to 10 visual analogue scale (VAS) by surgery-oriented clinicians with experience of > 50 surgeries for endometriosis. Results: The answers reflect the collective clinical experience of managing >10.000 women with endometriosis. Experience-based management was overall comparable as approved by >75% of answers rated ≥ 8/10 VAS. Knowledge-based management was more variable, reflecting debated issues and differences between experts and non-experts. Conclusions: The collective experience-based management of those with endometriosis is similar for surgery-oriented clinicians. Results do not conflict with EBM and are a Bayesian prior, to be confirmed, refuted or updated by further observations. What is new?: Collective experience-based management can be measured and is more than a personal opinion. This might extend EBM trial results to the entire population and add data difficult to obtain in RCTs, such as many aspects of surgery.

Reconsidering evidence-based management of endometriosis.

Background: Without an adequate animal model permitting experiments the pathophysiology of endometriosis remains unclear and without a non-invasive diagnosis, information is limited to symptomatic women. Lesions are macroscopically and biochemically variable. Hormonal medical therapy cannot be blinded since recognised by the patient and the evidence of extensive surgery is limited because of the combination of low numbers of interventions of variable difficulty with variable surgical skills. Experience is spread among specialists in imaging, medical therapy, infertility, pain and surgery. In addition, the limitations of traditional statistics and p-values to interpret results and the complementarity of Bayesian inference should be realised. Objectives: To review and discuss evidence in endometriosis management. Materials and Methods: A PubMed search for blinded randomised controlled trials in endometriosis. Results: Good-quality evidence is limited in endometriosis. Conclusions: Clinical experience remains undervalued especially for surgery. What is new?: Evidence-based medicine should integrate traditional statistical analysis and the limitations of P-values, with the complementary Bayesian inference which is predictive and sequential and more like clinical medicine. Since clinical experience is important for grading evidence, specific experience in the different disciplines of endometriosis should be used to judge trial designs and results. Finally, clinical medicine can be considered as a series of experiments controlled by the outcome. Therefore, the clinical opinion of many has more value than an opinion.

Bowel resection for deep endometriosis: a systematic review.

BACKGROUND: deep endometriosis involving the bowel often is treated by segmental bowel resection. In a recent review of over 10000 segmental bowel resections for indications other than endometriosis, low rectum resections, in particular, were associated with a high long-term complication rate for bladder, bowel and sexual function. OBJECTIVES: to review systematically segmental bowel resections for endometriosis for indications, outcome and complications according to the level of resection and the volume of the nodule. SEARCH STRATEGY: all published articles on segmental bowel resection for endometriosis identified through MEDLINE, EMBASE and ISI Web of Knowledge databases during 1997-2009. SELECTION CRITERIA: the terms 'bowel', 'rectal', 'colorectal', 'rectovaginal', 'rectosigmoid', 'resection' and 'endometriosis' were used. Articles describing more than five bowel resections for endometriosis, and with details of at least three of the relevant endpoints. DATA COLLECTION AND ANALYSIS: data did not permit a meaningful meta-analysis. MAIN RESULTS: thirty-four articles were found describing 1889 bowel resections. The level of bowel resection and the size of the lesions were poorly reported. The indications to perform a bowel resection were variable and were rarely described accurately. The duration of surgery varied widely and endometriosis was not always confirmed by pathology. Although not recorded prospectively, pain relief was systematically reported as excellent for the first year after surgery. Recurrence of pain was reported in 45 of 189 women; recurrence requiring reintervention occurred in 61 of 314 women. Recurrence of endometriosis was reported in 37 of 267 women. The complication rate was comparable with that of bowel resection for indications other than endometriosis. Data on sexual function were not found. CONCLUSIONS: after a systematic review, it was found that the indication to perform a segmental resection was poorly documented and the data did not permit an analysis of indication and outcome according to localisation or diameter of the endometriotic nodule. Segmental resections were rectum resections in over 90%, and the postoperative complication rate was comparable with that of resections for indications other than endometriosis. No data were found evaluating sexual dysfunction.

The severity and frequency distribution of endometriosis subtypes at different ages: a model to understand the natural history of endometriosis based on single centre/single surgeon data.

Background and Objective: to study the natural history of endometriosis. Materials and methods: the analysis of all women (n=2086) undergoing laparoscopy for pelvic pain and endometriosis between 1988 and 2011 at University Hospital Gasthuisberg. Main outcome measures: the severity of subtle, typical, cystic and deep endometriosis in adult women, with or without a pregnancy, as estimated by their pelvic area and their volume. Results: the number of women undergoing a laparoscopy increased up to 28 years of age and decreased thereafter. Between 24 and 44 years, the severity and relative frequencies of subtle, typical, cystic and deep lesions did not vary significantly. The number of women younger than 20 years was too small to ascertain the impression of less severe lesions. The severity of endometriosis lesions was not less in women with 1 or more previous pregnancies or with previous surgery. There was no bias over time since the type and severity of endometriosis lesions remained constant between 1988 and 2011. Conclusions: severity of endometriosis does not increase between 24 and 44 years of age, suggesting that growth is limited by intrinsic or extrinsic factors. Severity was not lower in women with a previous pregnancy. What is new: considering the time needed for lesions to become symptomatic together with the diagnostic delay, the decreasing number of laparoscopies after age 28 is compatible with a progressively declining risk of initiating endometriosis lesions after menarche, the remaining women being progessively less susceptible.

Preoperative imaging of deep endometriosis: pitfalls of a diagnostic test before surgery.

The usefulness of a test is determined by the clinical interpretation of its sensitivity and specificity. The pitfalls of a test with a surgical endpoint are described in this article, taking the diagnosis of deep endometriosis by imaging as an example, without discussing the management of deep endometriosis. Laparoscopy is not a 100% accurate "gold standard". Since it is not performed in women without symptoms, results are valid only for the group of women as specified in the indication for surgery. The confidence limits of accuracy estimations widen when accuracy is lower and when observations are less. Since positive and negative predictive values are inaccurate when prevalence of the disease is low, prevalence figures in the group of women investigated should be available. The accuracy of imaging should be stratified by clinically important aspects such as localisation and size of the lesion. The use of other variables as soft markers during ultrasonographic examination should be specified. It should be clear whether the accuracy of the test reflects symptoms and clinical examination and imaging combined, or whether the accuracy of the added value of imaging which requires Bayesian analysis. When imaging is used as an indication for surgery, circular reasoning should be avoided and the number of symptomatic women not undergoing surgery because of negative imaging should be reported. In conclusion, imaging reports should permit the clinician to judge the validity of the accuracy estimations of a diagnostic test, especially when used as an indication for surgery and when surgery is the gold standard to diagnose a disease.

Correction: Heterogeneity of endometriosis lesions requires individualisation of diagnosis and treatment and a different approach to research and evidence based medicine.

Statistical significance is used to analyse research findings and is together with biased free trials the cornerstone of evidence based medicine. However traditional statistics are based on the assumption that the population investigated is homogeneous without smaller hidden subgroups. The clinical, inflammatory, immunological, biochemical, histochemical and genetic-epigenetic heterogeneity of similar looking endometriosis lesions is a challenge for research and for diagnosis and treatment of endometriosis. The conclusions obtained by statistical testing of the entire group are not necessarily valid for subgroups. The importance is illustrated by the fact that a treatment with a beneficial effect in 80% of women but with exactly the same but opposite effect, worsening the disease in 20%, remains statistically highly significant. Since traditional statistics are unable to detect hidden subgroups, new approaches are mandatory. For diagnosis and treatment it is suggested to visualise individual data and to pay specific attention to the extremes of an analysis. For research it is important to integrate clinical, biochemical and histochemical data with molecular biological pathways and genetic-epigenetic analysis of the lesions.

Heterogeneity of endometriosis lesions requires individualisation of diagnosis and treatment and a different approach to research and evidence based medicine.

Statistical significance is used to analyse research findings and is together with biased free trials the cornerstone of evidence based medicine. However traditional statistics are based on the assumption that the population investigated is homogeneous without smaller hidden subgroups. The clinical, inflammatory, immunological, biochemical, histochemical and genetic-epigenetic heterogeneity of similar looking endometriosis lesions is a challenge for research and for diagnosis and treatment of endometriosis. The conclusions obtained by statistical testing of the entire group are not necessarily valid for subgroups. The importance is illustrated by the fact that a treatment with a beneficial effect in 80% of women but with exactly the same but opposite effect, worsening the disease in 20%, remains statistically highly significant. Since traditional statistics are unable to detect hidden subgroups, new approaches are mandatory. For diagnosis and treatment it is suggested to visualise individual data and to pay specific attention to the extremes of an analysis. For research it is important to integrate clinical, biochemical and histochemical data with molecular biological pathways and genetic-epigenetic analysis of the lesions.

Infection as a potential cofactor in the genetic-epigenetic pathophysiology of endometriosis: a systematic review.

BACKGROUND: The genetic-epigenetic theory postulates that endometriosis is triggered by a cumulative set of genetic-epigenetic (GE) incidents. Pelvic and upper genital tract infection might induce GE incidents and thus play a role in the pathogenesis of endometriosis. Thus, this article aims to review the association of endometriosis with upper genital tract and pelvic infections. METHODS: Pubmed, Scopus and Google Scholar were searched for 'endometriosis AND (infection OR PID OR bacteria OR viruses OR microbiome OR microbiota)', for 'reproductive microbiome' and for 'reproductive microbiome AND endometriosis', respectively. All 384 articles, the first 120 'best match' articles in PubMed for 'reproductive microbiome' and the first 160 hits in Google Scholar for 'reproductive microbiome AND endomytriosis' were hand searched for data describing an association between endometriosis and bacterial, viral or other infections. All 31 articles found were included in this manuscript. RESULTS: Women with endometriosis have a significantly increased risk of lower genital tract infection, chronic endometritis, severe PID and surgical site infections after hysterectomy. They have more colony forming units of Gardnerella, Streptococcus, Enterococci and Escherichia coli in the endometrium. In the cervix Atopobium is absent, but Gardnerella, Streptococcus, Escherichia, Shigella, and Ureoplasma are increased. They have higher concentrations of Escherichia Coli and higher concentrations of bacterial endotoxins in menstrual blood. A Shigella/Escherichia dominant stool microbiome is more frequent. The peritoneal fluid of women with endometriosis contains higher concentrations of bacterial endotoxins and an increased incidence of mollicutes and of HPV viruses. Endometriosis lesions have a specific bacterial colonisation with more frequently mollicutes (54%) and both high and medium-risk HPV infections (11%). They contain DNA with 96% homology with Shigella. In mice transplanted endometrium changes the gut microbiome while the gut microbiome influences the growth of these endometriosis lesions. CONCLUSIONS: Endometriosis is associated with more upper genital tract and peritoneal infections. These infections might be co-factors causing GE incidents and influencing endometriosis growth.

Hypomelanosis of Ito: electron microscopical observations on two new cases.

An ultrastructural study on two new cases of Ito's hypomelanosis is reported. According with previous studies on this pathological condition, a marked reduction of melanocytes is detected in the hypopigmented areas. In the proximity of preserved melanocytes, a nearly normal content of melanosomes is detected in basal keratinocytes. Melanocyte profiles are frequently located in close relationship with the basal lamina. An apparent increase of nerve endings is demonstrated at the dermo-epidermal edge. Nerve fibres show no pathological alterations. A functional impairement of the melanocytes is hypothesized, involving regressive changes and a tendence towards a round shape of their profiles. This could in part account for the prevalent basal location of the melanocytes. The role of the dermal nerve endings in the pathogenesis of the hypopigmented lesions is discussed.