Colorectal Cancer Diagnosis through Breath Test Using a Portable Breath Analyzer-Preliminary Data.

Screening methods available for colorectal cancer (CRC) to date are burdened by poor reliability and low patient adherence and compliance. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a non-invasive potential diagnostic tool for distinguishing CRC patients from healthy controls (HC). The aim of this study was to evaluate the reliability of an innovative portable device containing a micro-gas chromatograph in enabling rapid, on-site CRC diagnosis through analysis of patients' exhaled breath. In this prospective trial, breath samples were collected in a tertiary referral center of colorectal surgery, and analysis of the chromatograms was performed by the Biomedical Engineering Department. The breath of patients with CRC and HC was collected into Tedlar bags through a Nafion filter and mouthpiece with a one-way valve. The breath samples were analyzed by an automated portable gas chromatography device. Relevant volatile biomarkers and discriminant chromatographic peaks were identified through machine learning, linear discriminant analysis and principal component analysis. A total of 68 subjects, 36 patients affected by histologically proven CRC with no evidence of metastases and 32 HC with negative colonoscopies, were enrolled. After testing a training set (18 CRC and 18 HC) and a testing set (18 CRC and 14 HC), an overall specificity of 87.5%, sensitivity of 94.4% and accuracy of 91.2% in identifying CRC patients was found based on three VOCs. Breath biopsy may represent a promising non-invasive method of discriminating CRC patients from HC.

Thrombosed external hemorrhoids during pregnancy: surgery versus conservative treatment.

The management of thrombosed external hemorrhoids (TEH) during pregnancy is still under debate because of the fear of potential adverse effects on the fetus. This study aims to compare efficacy and safety of conservative versus surgical treatment of acute TEH in pregnant women. Furthermore, the outcome of two different surgical approaches was evaluated. This is a prospective observational study including a sub-analysis on two randomized groups of pregnant women affected by TEH. The primary outcome measured was the impact of conservative and surgical treatment defined in terms of VAS, clinical patient grading assessment scale (CPGAS) and the SF-12 questionnaire. In a randomized sub-analysis of the surgical treatment, the outcome of local excision (LE) versus thrombectomy (TE) was compared. Fifty-three patients entered the study. Twenty-six patients had conservative treatment and 22 underwent surgery. Within the surgical group, 8 were randomized for TE and 14 for LE. VAS, SF-12 and CPGAS improved in both groups after 3 and 10 days from the treatment. However, physical (PCS) and mental health (MCS) domains of the SF-12 and CPGAS showed a significant difference in favor of surgery on the 10th day (PCS: p < 0.002 and MCS: p = 0.03; CPGAS: p = 0.002). The surgical group showed an earlier significant reduction of pain on the 3rd day (p = 0.0004). In the surgical group, randomization was halted due to ethical concerns arising from a notable difference in the primary end point between subgroups during interim analysis. Specifically, the re-thrombosis rate was 38% (3/8) after TE and 7% (1/14) after LE. No complications occurred for either mothers or fetuses. Both surgical and conservative treatments are safe and effective. However, surgery allows a faster relief of anal pain. Thrombectomy is associated with higher risk of re-thrombosis when compared to local excision (clinicaltrials.gov ID number NCT04588467).

Undeserved authorship in surgical research: an underestimated bias with potential side effects on academic careers.

The incidence of courtesy authorship in research over time has probably increased due to the enormous pressure to publish to increase the bibliometric indexes necessary to achieve an academic role. The aim of this survey was to quantify and characterize this research malpractice among a very selected group of surgeons from different surgical specialties belonging to the European Association of Surgery (ESA). E-mail addresses for the invitation to take part to the survey were collected by the Twenty-eighth Annual Meeting final program. Five-item were designed and developed by the authors using an online platform. Eighty-six members from 21 countries completed the survey (female/male ratio: 0.09). In the last 10 years, almost half of the responders (41, 47.7%, 37 academics) have included colleagues for courtesy authorship. The most common reason of courtesy authorships was to support the academic career of another researcher (62.5%). Other reasons were fear of retaliation (12.5%), reciprocal authorship (12.5%) or support for a partner (10%). This survey showed that undeserved authorship is sadly confirmed to be a common research misconduct across any countries and medical specialties, even among a very selected group of surgeons with international reputation irrespective of the academic position.

Identification of a characteristic VOCs pattern in the exhaled breath of post-COVID subjects: are metabolic alterations induced by the infection still detectable?

SARS-CoV-2 is expected to cause metabolic alterations due to viral replication and the host immune response resulting in increase of cytokine secretion and cytolytic activity. The present prospective observational study is addressed at exploring the potentialities of breath analysis in discrimination between patients with a documented previous history of symptomatic SARS-CoV-2 infection and, at the moment of the enrollment, exhibiting a negative nasopharyngeal swab and acquired immunity (post-COVID) and healthy subjects with no evidence of previous SARS-CoV-2 infection (no-COVID). The main purpose is to understand if traces of metabolic alterations induced during the acute phase of the infection are still detectable after negativization, in the form of a characteristic volatile organic compound (VOC) pattern. An overall number of 60 volunteers aged between 25 and 70 years were enrolled in the study (post-COVID: n.30; no-COVID: n. 30), according to well-determined criteria. Breath and ambient air samples were collected by means of an automated sampling system (Mistral) and analyzed by thermal desorption-gas chromatography-mass spectrometry (TD-GC/MS). Statistical tests (Wilcoxon/Kruskal-Wallis test) and multivariate data analysis (principal component analysis (PCA), linear discriminant analysis) were performed on data sets. Among all compounds detected (76 VOCs in 90% of breath samples), 5 VOCs (1-propanol, isopropanol, 2-(2-butoxyethoxy)ethanol, propanal and 4-(1,1-dimethylpropyl)phenol) showed abundances in breath samples collected from post-COVID subjects significantly different with respect to those collected from no-COVID group (Wilcoxon/Kruskal-Wallis test,p-values <0.05). Although not completely satisfactory separation between the groups was obtained, variables showing significant differences between the two groups and higher loadings for PCA are recognized biomarkers of COVID-19, according to previous studies in literature. Therefore, based on the outcomes obtained, traces of metabolic alterations induced by SARS-CoV-2 infection are still detectable after negativization. This evidence raises questions about the eligibility of post-COVID subjects in observational studies addressed at the detection of COVID-19. (Ethical Committee Registration number: 120/AG/11).

Management and Treatment of External Hemorrhoidal Thrombosis.

Background: External hemorrhoidal thrombosis (EHT) is a common complication of hemorrhoidal disease. This condition causes extreme pain, likely resulting from internal anal sphincter hypertonicity, which traps the hemorrhoids below the dentate line thus leading to congestion and swelling. The choice of treatment remains controversial and both conservative and surgical options have been proposed in the last decades. Methods: This mini-review focuses on the most relevant studies found in literature evaluating conservative and surgical management of EHT. Special conditions such as pregnancy and EHT in elderly patients have been considered. Results: Traditionally, symptoms duration represents the discriminant in the choice between medical and surgical treatment. Several Coloproctological Societies considered conservative treatment as the first-line approach to EHT and a variety of options have been proposed: wait and see, mixture of flavonoids, mix of lidocaine and nifedipine, botulinum toxin injection and topical application of 0.2% glyceryl trinitrate. Meanwhile, different surgical treatments are recommended when EHT fails to respond to conservative management or when symptoms onset falls within the last 48-72 h: drainage with radial incision, conventional excision, excision under local anesthesia and stapled technique. Conclusion: The management and treatment of EHT is still controversial since no specific guidelines have been published. Both medical and surgical treatment have been proven effective but randomized clinical trials and structured consensus-based guidelines are warranted.

Cutting-Edge Research Trends in Colorectal Disease.

The scientific effort in improving colorectal disease treatment and outcomes has allowed for a continuous shift of burdens that were previously thought to be unassailable [...].

Quality of life meta-analysis following coloanal anastomosis versus abdominoperineal resection for low rectal cancer.

AIM: In low rectal cancers without sphincter involvement a permanent stoma can be avoided without compromising oncological safety. Functional outcomes following coloanal anastomosis (CAA) compared to abdominoperineal excision (APR) may be significantly different. This study examines all available comparative quality of life (QoL) data for patients undergoing CAA versus APR for low rectal cancer. METHODS: Published studies with comparative data on QoL outcomes following CAA versus APR for low rectal cancer were extracted from electronic databases. The study was registered with PROSPERO and adhered to PRISMA (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Data was combined using random-effects models. RESULTS: Seven comparative series examined QoL in 527 patients. There was no difference in the numbers receiving neoadjuvant radiotherapy in the APR and CAA groups (OR: 1.19, 95% CI: 0.78-1.81, p = 0.43). CAA was associated with higher mean scores for physical functioning(std mean diff -7.08, 95% CI: -11.92 to -2.25, p = 0.004) and body image (std. mean diff 11.11, 95% CI: 6.04-16.18, p < 0.0001). Male sexual problems were significantly increased in patients who had undergone APR compared to CAA (std. mean diff -16.20, 95% CI: -25.76 to -6.64, p = 0.0009). Patients who had an APR reported more fatigue, dyspnoea and appetite loss. Those who had a CAA reported higher scores for both constipation and diarrhoea. DISCUSSION: It is reasonable to offer a CAA to motivated patients where oncological outcomes will not be threatened. QoL outcomes appear to be superior when intestinal continuity is maintained, and permanent stoma avoided.

Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer.

We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAM10 underlies Trop-2-driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models. Overexpression of wild-type Trop-2 in KM12SM human colon cancer cells increased liver metastasis rates in vivo in immunosuppressed mice. Metastatic growth was further enhanced by a tail-less, activated ΔcytoTrop-2 mutant, indicating the Trop-2 tail as a pivotal inhibitory signaling element. In primary tumors and metastases, transcriptome analysis showed no down-regulation of CDH1 by transcription factors for epithelial-to-mesenchymal transition, thus suggesting that the pro-metastatic activity of Trop-2 is through alternative mechanisms. Trop-2 can tightly interact with ADAM10. Here, Trop-2 bound E-cadherin and stimulated ADAM10-mediated proteolytic cleavage of E-cadherin intracellular domain. This induced detachment of E-cadherin from ß-actin, and loss of cell-cell adhesion, acquisition of invasive capability, and membrane-driven activation of ß-catenin signaling, which were further enhanced by the ΔcytoTrop-2 mutant. This Trop-2/E-cadherin/ß-catenin program led to anti-apoptotic signaling, increased cell migration, and enhanced cancer-cell survival. In patients with colon cancer, activation of this Trop-2-centered program led to significantly reduced relapse-free and overall survival, indicating a major impact on progression to metastatic disease. Recently, the anti-Trop-2 mAb Sacituzumab govitecan-hziy was shown to be active against metastatic breast cancer. Our findings define the key relevance of Trop-2 as a target in metastatic colon cancer.

Systematic review with meta-analysis: volatile organic compound analysis to improve faecal immunochemical testing in the detection of colorectal cancer.

BACKGROUND: Faecal immunochemical test (FIT) is emerging as a valid test to rule-out the presence of colorectal cancer (CRC). However, the accuracy of FIT is dependent on the cut-off applied. An additional low-cost test could improve further detection of CRC. AIMS: To evaluate the efficacy of combined FIT and volatile organic compounds (VOC) in the detection of CRC within symptomatic populations. METHODS: Systematic reviews on the diagnostic accuracy of FIT and VOC, for the detection of CRC, were updated. Meta-analyses were performed adopting a bivariate model for sensitivity and specificity. Clinical utility of combined FIT and VOC was estimated using Fagan's nomogram. Post-test probability of FIT negatives was used as a pre-test probability for VOC. RESULTS: The pooled sensitivity and specificity of FIT at 10 µg/g faeces, for the detection of CRC, were 0.914 (95% confidence interval [CI] = 0.894-0.936) and 0.783 (CI = 0.850-0.696), respectively. For VOC, the sensitivity was 0.837 (CI = 0.781-0.881) and the specificity was 0.803 (CI = 0.870-0.712). The area under the curve for FIT and VOC were 0.926 and 0.885, respectively. In a population with 5% CRC prevalence, the estimated probability of having CRC following a negative FIT was 0.5% and following both negative FIT and VOC was 0.1%. CONCLUSIONS: In a FIT-negative symptomatic population, VOC can be a good test to rule-out the presence of CRC. The estimated probability reduction by 0.4% when both tests being negative offers adequate safety netting in primary care for the exclusion of CRC. The number needed to colonoscope to identify one CRC is eight if either FIT or VOC positive. Cost-effectiveness and clinical accuracy of this approach will need further evaluation.

Classifications and Clinical Assessment of Haemorrhoids: The Proctologist's Corner.

BACKGROUND: Haemorrhoidal disease (HD) is a benign condition affecting a considerable part of adult population. HD can be considered a social and economic burden with high impact on patients' lifestyle. Several new techniques and devices have been proposed for HD treatment; however, preoperative assessment is essential and the use of classification system is recommended. METHODS: In the last two decades many studies described the preoperative assessment and several attempts of classification for HD. This review focuses on the most relevant studies found in literature where classification systems and clinical evaluation with differential diagnosis have been evaluated. RESULTS: The knowledge of classification systems and differential diagnosis for HD has been shown to play a central role in the clinical assessment and the best treatment choice. Although there are new challenging techniques and devices for HD treatment, a preoperative assessment is always mandatory. CONCLUSION: Preoperative clinical evaluation is essential for HD patient treatment and outcome. Classification systems are useful for the therapeutic choice and researches on new medical or surgical treatments. In fact, the international guidelines advise several therapeutic options depending on the severity of the HD.

Pneumatosis Intestinalis and Hepatic Portal Venous Gas: Watch and Wait or Emergency Surgery? A Case Report and Literature Review.

BACKGROUND Hepatic portal venous gas (HPVG) associated with pneumatosis intestinalis (PI) can be indicative of several diseases, including inflammatory bowel disease (IBD), infective and obstructive gastrointestinal conditions, and also potentially life-threatening situations such as mesenteric ischemia. CASE REPORT A 60-year-old female patient came to our attention with evidence at computed tomography (CT) scan of gas in the portal vein and bowel walls with no sign of ischemia. General tenderness of the abdomen with absence of bowel sounds was detected at the physical examination. An exploratory laparotomy was performed with evidence of mesenteric ischemia. CONCLUSIONS Emergency surgery should be indicated when CT signs of PI and HPVG occur along with a clinical situation strongly suggestive of bowel ischemia, even with no radiological sign of this critical condition.

Functional outcome and quality of life evaluation of graciloplasty for the treatment of complex recto-vaginal and recto-urethral fistulas.

Recto-vaginal (RVF) and recto-urethral (RUF) fistulas are infrequent but disabling conditions that severely affect patients' quality of life. Considering the high recurrence rate after conservative approaches, the best surgical treatment is still challenging. The aim of this study was to evaluate the outcome of graciloplasty to treat patients with complex RVF or RUF, and to investigate its effect on the quality of life. Fourteen patients with RVF and RUF who underwent graciloplasty between 2003 and 2017 were retrospectively enrolled. The main outcome was the healing rate of fistulas. Postoperative patients satisfaction was evaluated administering the Clinical Patient Grading Assessment Scale (CPGAS), SF-36 questionnaires and Changes in Sexual Functioning (CSF) questionnaires. The Wexner score was calculated in case of preoperative faecal incontinence. RVF and RUF were iatrogenic in 11 patients and due to Crohn's disease in 3 cases. After 1 year of follow-up (IQR 10-14 months), the success rate of the procedure was 78%. Out of three patients with RVF due to Crohn's disease, two healed after the procedure. Six months after surgery, all eight SF-36 domains significantly improved except for "body pain"; CSF score significantly increased from 35.5 (IQR 31-38.7) to 44 (IQR 37.7-48.5); CPGAS score improved from a median value of 0 (IQR 0-0) to 4 (IQR 3.2-4). The Wexner score was calculated only in 5 patients with preoperative faecal incontinence and it significantly decreased from a median value of 12 (IQR 11-14) to 5 (IQR 4-5). Graciloplasty could be considered as a first option treatment for complex or recurrent RVF and RUF. It shows a good healing rate even in case of unfavourable factors like Crohn's disease.

The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function.

BACKGROUND: This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. METHODS: Twenty-nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face-to-face and three remote meetings to derive consensus between 2014 and 2018. KEY RECOMMENDATIONS: The IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia. CONCLUSIONS AND INFERENCES: This framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much-needed standardization to these techniques.

Diet After Cholecystectomy.

Patients with gallstones are often affected by alimentary disorders contributing to the onset of gallstones disease. Cholecystectomy can have nutritional and metabolic consequences in the short-term (diarrhea, abdominal pain and bloating) and in the long-term (increased Body Mass Index with metabolic syndrome, gastritis, liposoluble vitamin deficiency). Pathogenic mechanisms behind these disturbances are reviewed and the need for an early post-operative nutritional intervention based on low-lipid, high-fibers diet, is highlighted.