Family history as a major prerequisite for microsatellite instability screening in colorectal cancer is a poor selection tool.

Background: Deficient mismatch repair (MMR) leading to microsatellite instability (MSI) in tumors is thought to be present in over 15% of colorectal cancer (CRC) cases. Testing CRC for MSI has traditionally been recommended following the fulfillment of clinical criteria. However, the performance of clinical criteria, especially the family history, as a selection tool for MSI screening in CRC is questionable. Methods: We retrospectively investigated the incidence of high degree MSI (MSI-H) tumors in an unselected population of CRC patients and compared its prevalence between individuals with and without family history of cancers within the spectrum of MSI-H tumors as defined in the revised Bethesda criteria. Results: The study population included 274 patients, 70 with positive and 204 without family history of MSI-H tumors with complete data including findings from MSI analysis. The overall incidence of MSI-H CRC was 18.98%. There was no statistically significant difference in the incidence of MSI-H CRC amongst both groups. The sensitivity and specificity of family history with regard to the presence of an MSI-H tumor in this collective was 36.5% and 77.5%, respectively. Conclusions: A relevant number of cases with high MSI-H CRC may be missed secondary to screening based on clinical criteria like family history alone. Thus, systematic screening independent of clinical characteristics, especially family history of cancer should be recommended in all cases with CRC.

The role of mitochondrial damage-associated molecular patterns in acute pancreatitis.

Acute pancreatitis (AP) is one of the most common gastrointestinal tract diseases with significant morbidity and mortality. Current treatments remain unspecific and supportive due to the severity and clinical course of AP, which can fluctuate rapidly and unpredictably. Mitochondria, cellular power plant to produce energy, are involved in a variety of physiological or pathological activities in human body. There is a growing evidence indicating that mitochondria damage-associated molecular patterns (mtDAMPs) play an important role in pathogenesis and progression of AP. With the pro-inflammatory properties, released mtDAMPs may damage pancreatic cells by binding with receptors, activating downstream molecules and releasing inflammatory factors. This review focuses on the possible interaction between AP and mtDAMPs, which include cytochrome c (Cyt c), mitochondrial transcription factor A (TFAM), mitochondrial DNA (mtDNA), cardiolipin (CL), adenosine triphosphate (ATP) and succinate, with focus on experimental research and potential therapeutic targets in clinical practice. Preventing or diminishing the release of mtDAMPs or targeting the mtDAMPs receptors might have a role in AP progression.

Microsatellite instability is highly prevalent in older patients with colorectal cancer.

Background: Clinical guidelines suggest screening of colorectal cancer (CRC) for microsatellite instability (MSI). However, microsatellite instability-high (MSI-H) CRC is not rare in older patients. This study aimed to investigate the prevalence of MSI-H CRC in an unselected population in an age-based manner. Material and methods: A retrospective analysis of data from patients undergoing radical surgery for CRC was performed. Only cases with results from MSI testing using immunochemistry (IHC) were analyzed. Age-based analyses were performed using two cut-off ages: 50 years. as stated in Amsterdam II guidelines, and 60 years. as outlined in the revised Bethesda criteria. Results: The study population included 343 (146 female and 197 male) patients with a median age of 70 years (range 21-90 years). The prevalence of MSI-H tumors in the entire cohort was 18.7%. The prevalence of MSI-H CRC was 22.5% in the group ≤50 years vs. 18.2% in the group >50 years using the age limit in the Amsterdam II guidelines. MSI-H CRC was present in 12.6% of the group aged ≤60 years compared to 20.6% in the control group >60 years. Conclusion: MSI screening of CRC based on age alone is associated with negative selection of a relevant number of cases. MSI-H CRC is also common in elderly patients, who may be negatively selected secondary to an age-based screening algorithm. Following the results of this study, screening based on clinical criteria should be omitted in favor of systematic screening as is already internationally practiced.

[Quality of life of ostomates in Germany]. / Lebensqualität von Menschen mit einem künstlichen Darmausgang in Deutschland.

BACKGROUND: The presence of an ostomy may have a serious impact on the quality of life (QoL). The aim of this study was to evaluate the QoL of ostomates in Germany. METHOD: An online survey was performed using the validated Gastrointestinal Quality of Life Index (GIQLI) by Eypasch et al. Ostomates ≥ 18 yrs. with an ostomy duration ≥ 3 months were eligible to participate. RESULTS: Completed questionnaires from 519 participants (79.3 % female) with a median age of 50 yrs. (range 19-83 yrs.) and a median ostomy duration of 3 yrs. (range 3 months-58 yrs.) were analyzed. The most common indications for an ostomy were Crohn's disease (36.5 %), colorectal cancer (19.8 %) and ulcerative colitis (18.2 %). The mean GIQLI-Score in the study population was 94.8 ± 24.6, with higher scores corresponding with better QoL and healthy individuals reach 125.8. Limitations were recorded with regard to sleep, tiredness, energy level, endurance, fitness and sexuality. Individuals with a stoma due to Colitis (103,0 ± 24,5), colorectal cancer (99,2 ± 21,7) and Crohn's (95,0 ± 22,8) had the highest mean GIQLI-scores amongst all ostomates. DISCUSSION: The findings of this study confirm that ostomates have a reduced QoL compared to the healthy population. Amongst all ostomates, those with colitis, colorectal cancer and Crohn's have a better QoL compared to ostomy carriers with other diagnoses.

European Society of Coloproctology: Guidelines for diagnosis and treatment of cryptoglandular anal fistula.

AIM: The primary aim of the European Society of Coloproctology (ESCP) Guideline Development Group (GDG) was to produce high-quality, evidence-based guidelines for the management of cryptoglandular anal fistula with input from a multidisciplinary group and using transparent, reproducible methodology. METHODS: Previously published methodology in guideline development by the ESCP has been replicated in this project. The guideline development process followed the requirements of the AGREE-S tool kit. Six phases can be identified in the methodology. Phase one sets the scope of the guideline, which addresses the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula in adult patients presenting to secondary care. The target population for this guideline are healthcare practitioners in secondary care and patients interested in understanding the clinical evidence available for various surgical interventions for anal fistula. Phase two involved formulation of the GDG. The GDG consisted of 21 coloproctologists, three research fellows, a radiologist and a methodologist. Stakeholders were chosen for their clinical and academic involvement in the management of anal fistula as well as being representative of the geographical variation among the ESCP membership. Five patients were recruited from patient groups to review the draft guideline. These patients attended two virtual meetings to discuss the evidence and suggest amendments. In phase three, patient/population, intervention, comparison and outcomes questions were formulated by the GDG. The GDG ratified 250 questions and chose 45 for inclusion in the guideline. In phase four, critical and important outcomes were confirmed for inclusion. Important outcomes were pain and wound healing. Critical outcomes were fistula healing, fistula recurrence and incontinence. These outcomes formed part of the inclusion criteria for the literature search. In phase five, a literature search was performed of MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews by eight teams of the GDG. Data were extracted and submitted for review by the GDG in a draft guideline. The most recent systematic reviews were prioritized for inclusion. Studies published since the most recent systematic review were included in our analysis by conducting a new meta-analysis using Review manager. In phase six, recommendations were formulated, using grading of recommendations, assessment, development, and evaluations, in three virtual meetings of the GDG. RESULTS: In seven sections covering the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula, there are 42 recommendations. CONCLUSION: This is an up-to-date international guideline on the management of cryptoglandular anal fistula using methodology prescribed by the AGREE enterprise.

Relationship between Cholesterol-Related Lipids and Severe Acute Pancreatitis: From Bench to Bedside.

It is well known that hypercholesterolemia in the body has pro-inflammatory effects through the formation of inflammasomes and augmentation of TLR (Toll-like receptor) signaling, which gives rise to cardiovascular disease and neurodegenerative diseases. However, the interaction between cholesterol-related lipids and acute pancreatitis (AP) has not yet been summarized before. This hinders the consensus on the existence and clinical importance of cholesterol-associated AP. This review focuses on the possible interaction between AP and cholesterol-related lipids, which include total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) A1, from the bench to the bedside. With a higher serum level of total cholesterol, LDL-C is associated with the severity of AP, while the persistent inflammation of AP is allied with a decrease in serum levels of cholesterol-related lipids. Therefore, an interaction between cholesterol-related lipids and AP is postulated. Cholesterol-related lipids should be recommended as risk factors and early predictors for measuring the severity of AP. Cholesterol-lowering drugs may play a role in the treatment and prevention of AP with hypercholesterolemia.

Damage associated molecular patterns and neutrophil extracellular traps in acute pancreatitis.

Previous researches have emphasized a trypsin-centered theory of acute pancreatitis (AP) for more than a century. With additional studies into the pathogenesis of AP, new mechanisms have been explored. Among them, the role of immune response bears great importance. Pro-inflammatory substances, especially damage-associated molecular patterns (DAMPs), play an essential role in activating, signaling, and steering inflammation. Meanwhile, activated neutrophils attach great importance to the immune defense by forming neutrophil extracellular traps (NETs), which cause ductal obstruction, premature trypsinogen activation, and modulate inflammation. In this review, we discuss the latest advances in understanding the pathological role of DAMPs and NETs in AP and shed light on the flexible crosstalk between these vital inflammatory mediators. We, then highlight the potentially promising treatment for AP targeting DAMPs and NETs, with a focus on novel insights into the mechanism, diagnosis, and management of AP.

The effect of preoperative stoma site marking on risk of stoma-related complications in patients with intestinal ostomy - A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis aimed to investigate the effect of preoperative stoma site marking on stoma-related complications in patients with intestinal ostomy. METHODS: MEDLINE, Embase, CENTRAL, CINHAL, and Google Scholar were searched up to August 2021 for randomised controlled trials (RCTs) and nonrandomised studies of interventions (NRSI) that involved patients with intestinal ostomies comparing preoperative stoma site marking to no marking and which reported at least one patient-relevant outcome. Outcomes were prioritised by stakeholder involvement. Random-effects meta-analyses produced odds ratios (ORs) or standardised mean differences (SMD) and 95% confidence intervals (CIs). The ROBINS-I tool and the GRADE approach were used to assess the risk of bias and certainty of evidence, respectively. RESULTS: This review included two RCTs and 25 NRSI. The risk of bias was high in RCTs and serious to critical in NRSI. Although preoperative site marking reduced stoma-related complications (OR: 0.45, 95% CI: [0.31-0.65]), dependence on professional or unprofessional care (narrative synthesis), and increased health-related quality of life (SMD: 1.13 [0.38-1.88]), the evidence is very uncertain. Preoperative site marking may probably reduce leakage (OR: 0.14 [0.06-0.37]) and may decrease dermatological complications (OR: 0.38 [0.29-0.50]) and surgical revision (OR: 0.09 [0.02-0.49]). The confidence in the cumulative evidence was moderate to very low. CONCLUSION: Despite low quality evidence, preoperative stoma site marking can prevent stoma-related complications and should be performed in patients undergoing gastrointestinal surgery given that this intervention poses no harm to patients.

The safety of surgical technique for ileostomy and colostomy in preventing parastomal hernias: an in vitro experimental simulation study.

BACKGROUND: Parastomal hernia (PH) is a common long-term complication in persons with an ostomy. Although the cause of PH may be multifactorial, the surgical technique employed for the creation of a stoma may be a risk factor for the development of PH. The traditional technique of cruciate fascia incision may predispose to increased pressure zones at the ostomy exit site, thereby increasing the risk of PH. A circular excision of the abdominal fascia at the ostomy exit site enables a uniform pressure distribution, thereby reducing the risk of PH. This hypothesis was tested in this in vitro experimental simulation study. METHODS: The effect of the surgical technique for ostomy creation on the risk of PH development was investigated in this in vitro experimental simulation study. The pressure development at the stoma site was compared for the traditional cruciate incision vs. circular fascia excision. RESULTS: The pressure at the ostomy site was about four-times higher in the tradition cruciate incision technique compared to the circular excision technique. This finding was independent of unilateral (e.g. peritoneal) pressure application. CONCLUSION: The main finding from this study suggests that the traditional cruciate incision of the abdominal fascia for the creation of an intestinal ostomy predisposes to increased pressures at the ostomy site, thus increasing the risk of PH. This effect is not seen in the experimental setting following a circular excision of the fascia. Thus, this surgical aspect may be adopted as a possible means of reducing the risk of parastomal hernia in patients undergoing ostomy surgery.

The role of saline irrigation prior to wound closure in the reduction of surgical site infection: a systematic review and meta-analysis.

BACKGROUND: Surgical site infection (SSI) describes an infectious complication of surgical wounds. Although SSI is thought to be preventable, it still represents a major cause of morbidity and substantial economic burden on the health system. Wound irrigation (WI) might reduce the level of bacterial contamination, but current data on its role in reducing or preventing SSI is conflicting. Our aim was to investigate the effectiveness of WI with normal saline prior to wound closure for the reduction of SSI in patients undergoing abdominal surgery. METHODS: We conducted a systematic literature search in MEDLINE, EMBASE, and CENTRAL from inception to present, and cross-checked the reference lists of all included primary studies and relevant systematic reviews. (Quasi-) randomized controlled trials (RCTs) investigating the rate of SSI when using normal saline vs. no irrigation prior to wound closure following abdominal surgery were included. Primary outcome was the rate of SSI, secondary outcome the mean length of hospital stay (LOS). RESULTS: Four RCTs including a total of 1194 patients were included for analysis. All studies compared wound irrigation with normal saline with no wound irrigation prior to wound closure. Their risk of bias was moderate. The relative risk of developing a SSI was lower when wound irrigation with normal saline was performed prior to wound closure although the effect was not statistically significant (risk ratio 0.73, 95%-confidence level: 0.37 to 1.43). Similarly, there was no difference in the LOS amongst both intervention arms. CONCLUSION: This systematic review could not identify an advantage for routine irrigation of abdominal wounds with normal saline over no irrigation prior to wound closure in preventing or reducing the rate of SSI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registry number CRD42018082287 .

Peritoneal spillage is not an issue in patients undergoing minimally invasive surgery for colorectal cancer.

BACKGROUND: Surgery for colorectal cancer (CRC) is increasingly being performed via the minimally invasive route. However, reports of postoperative wound and port site seeding as well as peritoneal spillage have been worrisome. We investigated the risk of peritoneal spillage in patients undergoing laparoscopic surgery for CRC. METHODS: Cytology specimens were gained from the retrieval bag following intracorporeal resection and specimen retrieval using an endoscopic retrieval bag. Histopathologic examination of the cytology specimens was performed for the presence of malignant cells. RESULTS: Cytology specimens of 73 (34 female and 39 male) consecutive patients with a median age of 71 years were included for analysis. Advanced CRC in stages III and IV was present in 41% of the study population. Malignant cells were not found in any specimen. CONCLUSION: Laparoscopic oncologic resection of colorectal cancer is not a risk factor for peritoneal spillage. Minimally invasive oncologic colorectal resection is safe without the increased risk of peritoneal carcinomatosis.

Routine preoperative mechanical bowel preparation with additive oral antibiotics is associated with a reduced risk of anastomotic leakage in patients undergoing elective oncologic resection for colorectal cancer.

BACKGROUND: Anastomotic leakage (AL) following colorectal resection is a serious issue. AL in oncologic patients might negatively affect the overall survival. Recently, mechanical bowel preparation with additive oral antibiotics (MBP + AB) prior to surgery has been suggested as a means of reducing AL. However, it is unclear whether this positive effect is secondary to MBP alone or secondary to the additive oral antibiotic (MBP + AB). The aim of this study was to investigate the effect of mechanical bowel preparation with additive oral antibiotics (MBP + AB) and without additive oral antibiotics (MBP - AB) on the rate of AL following colorectal resection for cancer. MATERIALS AND METHODS: Patients undergoing surgical management for colorectal cancer with anastomosis from January 2014 till September 2017 were included for analysis. Cases undergoing MBP + AB were included in the study group. Patients undergoing MBP - AB were included in the control group. Both groups were compared with regard to the rate of AL. RESULTS: Four hundred and ninety-six patients: 125 undergoing MBP + AB and 371 undergoing MBP - AB were included for analysis. Significantly, more male patients were included in the MBP - AB group compared to the MBP + AB group: 60.1% vs. 45.6% respectively (p = 0.03). Both groups were similar with regard to age distribution and clinicopathological findings (p > 0.05). The rate of AL was significantly higher in the control group (MBP - AB) compared to study group (MBP + AB) (9.1% vs. 4.0%, p = 0.03). CONCLUSION: Mechanical bowel preparation with additive oral antibiotics prior to elective colorectal resection with anastomosis significantly reduces the risk of AL. Therefore, mechanical bowel preparation with additive non-absorbable oral antibiotics should be recommended in all cases prior to elective colorectal surgery.

The role of indocyanine green fluoroscopy for intraoperative bile duct visualization during laparoscopic cholecystectomy: an observational cohort study in 70 patients.

BACKGROUND: Bile duct injury is the most feared complication during laparoscopic cholecystectomy. Real-time intraoperative imaging using indocyanine green (ICG) might reduce the risk of bile duct injury by improving visualization of the biliary tree during laparoscopic cholecystectomy. We compared the outcomes of laparoscopic cholecystectomy in patients with and without real-time ICG. METHODS: A retrospective analysis of the data of patients undergoing laparoscopic cholecystectomy with and without ICG in a referral centre for minimally invasive surgery was performed. We hypothesized that laparoscopic cholecystectomy with real-time ICG enables a better identification of the biliary tree and thus increases surgical safety. The outcomes of laparoscopic cholecystectomy with and without ICG were compared using the duration of surgery, the rate of bile duct injury, the rate of conversion, complications and the length of stay. RESULTS: Seventy patients including 29 with and 41 without ICG underwent laparoscopic cholecystectomy within the period of investigation. The median duration of surgery was 53.0 vs. 54.0 min while the median length of stay was 2.0 d in the group with and without ICG respectively. The rate of conversion was 2.4% in the group without ICG, while no conversion was performed in the group with ICG. NO bile duct injury occurred in both groups. These differences were not statistically significant. CONCLUSION: Laparoscopic cholecystectomy with real-time indocyanine green fluorescence cholangiography enables a better visualization and identification of biliary tree and therefore should be considered as a means of increasing the safety of laparoscopic cholecystectomy.

The role of saline irrigation prior to wound closure in the reduction of surgical site infection: protocol for a systematic review and meta-analysis.

BACKGROUND: Surgical site infection describes an infectious complication of surgical wounds. This single complication is thought to occur in close to 20% of surgical cases. This complication has been described in all kinds of surgical procedure including minimally invasive procedures. Wound irrigation is frequently used as a means of reducing surgical site infection. However, there is lack of solid evidence to support routine wound irrigation. The aim of this review is to provide evidence for the efficacy of routine wound irrigation with normal saline in preventing surgical site infection. The rate of surgical site infection in cases with and without wound irrigation will be analyzed. METHODS/DESIGN: Systematic literature searches will be conducted to identify all published and unpublished studies. The following databases will be searched for citations from inception to present: MEDLINE (via PubMed), Embase (via Embase), and CENTRAL (via the Cochrane library). The search strategy will be developed by the research team in collaboration with an experienced librarian and checked by a referee according to the Peer Review of Electronic Search Strategies (PRESS) guideline. A draft of the PubMed search strategy could be (irrigation[tiab] OR "Therapeutic Irrigation"[mesh] OR lavage[tiab]) AND (saline[tiab] OR "Sodium Chloride"[mesh] OR sodium chloride[tiab]) NOT ("Comment" [Publication Type] OR "Letter" [Publication Type] OR "Editorial" [Publication Type]). No time limits will be set. The reference lists of eligible articles will be hand searched. Relevant data will be extracted from eligible studies using a previously designed data extraction sheet. Relative risks will be calculated for binary outcomes and mean differences or standardized mean differences, if necessary, for continuous outcomes. For all measures, 95% confidence levels will be calculated. Both arms would be compared with regard to the rate of surgical site infection within 30 days following surgery. We will report the review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. DISCUSSION: This review aims at investigating the value of routine wound irrigation using normal saline in preventing surgical site infection. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42018082287.

Intraoperative real-time fluorescence angiography with indocyanine green for evaluation of intestinal viability during surgery for an incarcerated obturator hernia: a case report.

BACKGROUND: Bowel incarceration represents a dreaded complication amongst patients with hernias. The intraoperative evaluation of the bowel perfusion following hernia reduction with regard to the need for resection of ischaemic bowel can be challenging. In this case report we discuss intraoperative fluorescence angiography with indocyanine green (ICG) as an objective means of accessing bowel perfusion following hernia reduction. CASE PRESENTATION: The case of a 92-year-old, caucasian, female patient presenting with symptoms of small bowel obstruction secondary to an incarcerated left sided obturator hernia is presented. An incarcerated segment of the small bowel was reduced during emergency laparoscopy. Intraoperative ICG fluorescence angiography revealed ischaemic changes in the normal appearing bowel, so that the involved segment was resected. The postoperative course was uneventful and the patient was discharged home safely on postoperative day seven. CONCLUSION: Intraoperative ICG fluorescence angiography provides an objective method of judging bowel perfusion and therefore represents a useful tool for assessing intestinal perfusion in patients with incarcerated hernia.

Intestinal Ostomy.

BACKGROUND: About 100 000 ostomy carriers are estimated to live in Germany today. The creation of an ostomy represents a major life event that can be associated with impaired quality of life. Optimal ostomy creation and proper ostomy care are crucially important determinants of the success of treatment and of the patients' quality of life. METHODS: This article is based on pertinent publications retrieved by a selective search in PubMed, GoogleScholar, and Scopus, and on the authors' experience. RESULTS: Intestinal stomata can be created using either the small or the large bowel. More than 75% of all stomata are placed as part of the treatment of colorectal cancer. The incidence of stoma-related complications is reported to be 10-70%. Skin irritation, erosion, and ulceration are the most common early complications, with a combined incidence of 25-34%, while stoma prolapse is the most common late complication, with an incidence of 8-75%. Most early complications can be managed conservatively, while most late complications require surgical revision. In 19% of cases, an ostomy that was initially planned to be temporary becomes permanent. Inappropriate stoma location and inadequate ostomy care are the most common causes of early complications. Both surgical and patient-related factors influence late complications. CONCLUSION: Every step from the planning of a stoma to its postoperative care should be discussed with the patient in detail. Preoperative marking is essential for an optimal stoma site. Optimal patient management with the involvement of an ostomy nurse increases ostomy acceptance, reduces ostomy-related complications, and improves the quality of life of ostomy carriers.