No evidence for fixation of mesh in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the differences in hernia recurrence and chronic postoperative inguinal pain (CPIP) in randomized, controlled trials comparing fixation and non-fixation of the mesh in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair. METHODS: A multi-database systematic search was conducted for randomized, controlled trials comparing fixation versus non-fixation of the mesh in TAPP inguinal hernia repair. All eligible papers were assessed for risk of bias using the revised Cochrane risk of bias tool for randomized trials (RoB 2.0). Quality of evidence was evaluated using the GRADE system. Meta-analyses were performed regarding recurrence and CPIP using RevMan. RESULTS: Seven prospective, randomized controlled trials were included. Laparoscopic TAPP inguinal hernia repair was performed in 1732 patients with 737 procedures performed without fixation and 995 procedures with fixation of the mesh. Despite all trials being RCTs, the trials were limited by substantial bias and the quality of evidence was low regarding hernia recurrence and very low regarding CPIP. Pooled estimates from meta-analyses were an OR of 2.80 (95% CI 0.61-12.77) for hernia recurrence and a mean difference in visual analogue scale (VAS) of 0.17 (95% CI 0.90-1.24) for CPIP, respectively. CONCLUSION: The current evidence is very uncertain and mesh fixation may have little to no effect regarding hernia recurrence and chronic postoperative inguinal pain in patients operated with TAPP inguinal hernia repair.

Personalized circulating tumor DNA in patients with hepatocellular carcinoma: a pilot study.

BACKGROUND: Mutational analysis of circulating tumor DNA (ctDNA) can potentially be used for early detection of recurrence after resection for hepatocellular carcinoma (HCC). Mutations from tumor may be identified in plasma as an early sign of recurrence. We conducted a pilot study investigating if somatic mutations could be detected in plasma in patients undergoing liver resection for HCC and in patients with advanced non-resectable HCC. METHODS AND RESULTS: We prospectively included patients undergoing curative liver resection for HCC. Tumor tissue was investigated with whole exome sequencing and preoperative blood samples were evaluated for ctDNA using targeted next-generation sequencing (NGS) with TruSight Oncology 500 including 523 cancer-associated genes. Subsequently, the method was evaluated in patients with advanced HCC. We included eight patients curatively resected for HCC, where tumor tissue mutations were identified in seven patients. However, only in one patient tumor specific mutations were found in the preoperative blood sample. In all three patients with advanced HCC, tumor mutations were detected in the blood. CONCLUSIONS: In patients with resectable HCC, ctDNA could not be reliably detected using the applied targeted NGS method. In contrast, ctDNA was detected in all patients with advanced HCC. Small tumors, tumor heterogeneity and limited sequencing coverage may explain the lack of detectable ctDNA.

No difference in sexual dysfunction after transabdominal preperitoneal (TAPP) approach for inguinal hernia with fibrin sealant or tacks for mesh fixation.

BACKGROUND: Postoperative sexual dysfunction in relation to laparoscopic groin hernia surgery may be related to methods of mesh fixation. However, this has not been investigated earlier. Moreover, results regarding sexual dysfunction in females have not been reported systematically. The aim of this study was to compare fibrin sealant versus tacks for fixation of mesh regarding sexual dysfunction in males and females. METHODS: Using the Danish Hernia Database, patients operated laparoscopically for groin hernia with a transabdominal preperitoneal (TAPP) procedure with fibrin sealant or tacks for mesh fixation were sent a questionnaire regarding sexual dysfunction. Sexually active patients without recurrence were evaluated in this study. RESULTS: Pain during sexual activity was present in 115 of 1019 (11.3 %) males and 17 of 147 (11.6 %) females. There was no difference between fibrin sealant and tacks for mesh fixation and no difference between genders. Pain intensity, characteristics and origin were comparable between fibrin sealant and tacks for both genders. We found a relationship between a higher rate of sexual dysfunction and lower age for both genders. CONCLUSION: We found no difference between fibrin sealant and tacks in pain during sexual activity or intensity of pain. However, younger age may be a risk factor for pain during sexual activity. Considering the high rate of postoperative sexual dysfunction, it is important to include this topic in the preoperative patient information.

Advanced age is a risk factor for proximal adenoma recurrence following colonoscopy and polypectomy.

BACKGROUND: Knowledge of risk factors for recurrence of colorectal adenomas may identify patients who could benefit from individual surveillance strategies. The aim of this study was to identify risk factors for recurrence of colorectal adenomas in a high-risk population. METHODS: Data were used from a randomized clinical trial that showed no effect of aspirin-calcitriol-calcium treatment on colorectal adenoma recurrence. Patients at high risk of colorectal cancer who had one or more sporadic colorectal adenomas removed during colonoscopy were followed up for 3 years. Independent risk factors associated with recurrence and characteristics of recurrent adenomas were investigated in a generalized linear model. RESULTS: After 3 years, the recurrence rate was 25·8 per cent in 427 patients. For younger subjects (aged 50 years or less), the recurrence rate was 19 per cent; 18 of 20 recurrent adenomas were located in the distal part of the colon. For older subjects (aged over 70 years), the recurrence rate was 35 per cent, and 16 of 25 recurrent adenomas were in the proximal colon. Age (odds ratio (OR) 1·04, 95 per cent c.i. 1·01 to 1·07) and number of adenomas (OR 1·27, 1·11 to 1·46) at the time of inclusion in the study were independent risk factors for recurrence. CONCLUSION: In contrast to current guidelines, advanced age is not a reason to discontinue adenoma surveillance in patients with an anticipated live expectancy in which recurrence can arise.

The prevalence of umbilical and epigastric hernia repair: a nationwide epidemiologic study.

PURPOSE: Umbilical and epigastric hernia repair are common surgical procedures; however, the nationwide gender and age-specific prevalence of these repairs is unknown, and this knowledge could form the basis for new studies. METHODS: A nationwide register-based study covering all people living in Denmark on December 31st, 2010 was performed. Within this population all umbilical and epigastric hernia repairs from January 1st, 2006 to December 31st, 2010 were identified using data from the Danish National Hospital Register, and 5-year prevalence estimates were calculated. RESULTS: The study population covered 5,639,885 persons (49 % males). A total of 10,107 patients (68 % males) were operated for an umbilical hernia and 2412 patients (55 % males) were operated for an epigastric hernia. The age-specific 5-year prevalence differed for both hernia types. The highest 5-year prevalence of umbilical hernia repairs was seen in males aged 60-70 years with a 5-year prevalence of 0.53 % (95 % CI 0.51-0.56 %) and the highest age-specific 5-year prevalence of epigastric hernia repair was seen in 40-50 year females with a 5-year prevalence of 0.086 % (95 % CI 0.077-0.095 %). CONCLUSION: The gender and age-specific 5-year prevalence of umbilical and epigastric hernia repair differed in a nationwide population.

Possible benefits of robot-assisted rectal cancer surgery regarding urological and sexual dysfunction: a systematic review and meta-analysis.

AIM: Robot-assisted surgery for rectal cancer may result in lower rates of urogenital dysfunction compared with laparoscopic surgery. A systematic review was conducted of studies reporting urogenital dysfunction after robot-assisted rectal cancer surgery. METHOD: PubMed, Embase and the Cochrane Library were systematically searched in February 2014. All studies investigating urogenital function after robot-assisted rectal cancer surgery were identified. The inclusion criteria for meta-analysis studies required comparison of robot-assisted with laparoscopic surgery and the evaluation of urological and sexual function by validated questionnaire. The outcome was evaluated using the International Prostate Symptom Score (IPSS), the International Index of Erectile Function (IIEF) and the Female Sexual Function Index. RESULTS: Ten studies including 689 patients were included. For the meta-analysis this fell to four including 152 patients in the robotic group and 161 in the laparoscopic group, without heterogeneity. The IPSS score at 3 and 12 months favoured robot-assisted surgery [mean difference (MD) -1.58; 95% CI (-3.1, -0.0), [P = 0.04; and MD -0.90 (-1.81, -0.02), P = 0.05]. IIEF scores at 3 months' follow-up [MD -2.59 (-4.25, -0.94),] P = 0.002] and 6 months' follow-up [MD -3.06 (-4.53, -1.59), P = 0.0001] were better after robot-assisted than laparoscopic surgery. CONCLUSION: Although there were few data and no randomized controlled trials the results of the review suggested that robot-assisted surgery resulted in improved urogenital function than after laparoscopy.

The diagnostic value of a panel of serological markers in acute appendicitis.

BACKGROUND: Appendicitis is a frequent reason for hospital admissions. Elevated C-reactive protein, white blood cell count, and serum bilirubin have been suggested as individual markers for appendicitis and appendiceal perforation. The aim of this study was to analyze if a combination of serologic markers could increase the prognostic accuracy of diagnosing non-perforated and perforated appendicitis. MATERIAL AND METHODS: Demographic data, histological findings, blood tests, and clinical symptoms were collected on all patients who underwent a diagnostic laparoscopy, a laparoscopic appendectomy, or conventional (open) appendectomy between May 2009 and May 2012 from a surgical department. The patients were grouped into those with either perforated appendicitis, non-perforated appendicitis, or differential diagnosis. Univariate and multivariate models were used to identify which markers were useful in predicting acute and perforated appendicitis, and receiving operating characteristics curves were used to find the specificity, sensitivity, and the negative and positive predictive values. RESULTS: A total of 1008 patients were operated under suspicion of appendicitis. From these, 700 patients had a pathologically verified inflamed appendix and 190 had a perforated appendix. Patients with acute appendicitis had significantly higher blood levels of white blood cell, bilirubin, C-reactive protein, and alanine transaminase than patients without appendicitis. Patients with perforated appendicitis had significantly higher levels of white blood cell, bilirubin, and C-reactive protein than patients with non-perforated appendicitis. The highest positive predictive value to discriminate between acute appendicitis and non-appendicitis was of a linear regression model combining white blood cell count, bilirubin, and alanine transaminase. C-reactive protein levels and a linear regression model, including white blood cell count, bilirubin, and C-reactive protein levels as variables, had the highest negative predictive values when discriminating between perforated and non-perforated appendicitis. CONCLUSION: Combining blood markers was useful in predicting appendicitis and perforated appendicitis. In addition to C-reactive protein and white cell count, blood levels of bilirubin, and alanine transaminase may be useful.

Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.

Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.

Preoperative risk factors for anastomotic leakage after resection for colorectal cancer: a systematic review and meta-analysis.

AIM: Colorectal anastomotic leakage is a serious complication. Despite extensive research, no consensus on the most important preoperative risk factors exists. The aim of this systematic review and meta-analysis was to evaluate risk factors for anastomotic leakage in patients operated with colorectal resection. METHOD: The databases MEDLINE, Embase and CINAHL were searched for prospective observational studies on preoperative risk factors for anastomotic leakage. Meta-analyses were performed on outcomes based on odds ratios (OR) from multivariate regression analyses. The Newcastle-Ottawa scale was used for bias assessment within studies, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for quality assessment of evidence on outcome levels. RESULTS: This review included 23 studies evaluating 110,272 patients undergoing colorectal resection for cancer. The meta-analyses found that a low rectal anastomosis [OR = 3.26 (95% CI: 2.31-4.62)], male gender [OR = 1.48 (95% CI: 1.37-1.60)] and preoperative radiotherapy [OR = 1.65 (95% CI: 1.06-2.56)] may be risk factors for anastomotic leakage. Primarily as a result of observational design, the quality of evidence was regarded as moderate or low for these risk factors according to the GRADE approach. CONCLUSION: Based on the best available evidence, important preoperative risk factors for colorectal anastomotic leakage have been identified. Knowledge on risk factors may influence treatment and procedure-related decisions, and possibly reduce the leakage rate.

No consensus on restrictions on physical activity to prevent incisional hernias after surgery.

PURPOSE: In the postoperative phase after colorectal surgery, restrictions on physical activity are often recommended for patients to prevent incisional hernias. However, evidence does not support that restrictions may prevent such hernias. The purpose of this study was to evaluate the extent of restrictions on physical activity recommended for patients operated for colorectal cancer and to evaluate the agreement among surgical specialists. METHODS: A questionnaire was sent to 60 general surgeons (specialists) in Denmark and Sweden working in academic departments of surgery with a high volume of colorectal cancer resections. The questionnaire was case based and contained questions regarding possible restrictions on physical activity recommended for patients 0-2, 2-6 and >6 weeks after resection for colorectal cancer. Agreement among the surgeon on whether restrictions should be recommended was analyzed. RESULTS: Forty-one surgeons answered the questionnaire (68.3 %). The probability that two randomly chosen specialists agreed on whether restrictions should be given was generally low for the first two time periods (0-2 and 2-6 weeks); however, at >6 weeks there was a high level of agreement. Moreover, the number of restrictions recommended was different between the 41 surgeons (p < 0.0005) and more restrictions were recommended for open compared with laparoscopic surgery (p < 0.0005). CONCLUSIONS: Major disagreements exist on the degree of restrictions on physical activity that should be recommended for patients after colorectal surgery. As there is no evidence to support that specific restrictions prevent hernia formation, these are merely based on personal preferences. Clinical studies in this area are therefore highly warranted.

Oral chemoprevention with acetyl salicylic Acid, vitamin D and calcium reduces the risk of tobacco carcinogen-induced bladder tumors in mice.

Bladder cancer is a common urological malignancy with high recurrence rate, which may be reduced by chemoprevention. The aim was to evaluate chemoprevention in a mouse model of tobacco carcinogen-induced bladder tumors. A total of 60 A/J mice were randomized to normal diet, diet with low calcium, and diet with chemoprevention (acetyl salicylic acid, 1-alpha 25(OH)2-vitamin D3 and calcium). There were significantly fewer tumors (0 (0-0) vs. 0 (0-2), p = .045) and fewer animals with tumors (0/20 vs. 5/20, p = .045) in the chemoprevention group compared with controls. Thus, chemoprevention diet effectively reduced the tumor promoting effect of tobacco carcinogens in the mouse bladder.

An experimental animal model for abdominal fascia healing after surgery.

BACKGROUND: Incisional hernia (IH) is a well-known complication after abdominal surgical procedures. The exact etiology of IH is still unknown even though many risk factors have been suggested. The aim of this study was to create an animal model of a weakly healed abdominal fascia that could be used to evaluate the actively healing fascia. Such an animal model may promote future research in the prevention of IH. METHODS: 86 male Sprague-Dawley rats were used to establish a model involving six experiments (experiments A-F). Mechanical testing of the breaking strength of the healed fascia was performed by testing tissue strips from the healed fascia versus the unincised control fascia 7 and 28 days postoperatively. RESULTS: During the six experiments a healing model was created that produced significantly weaker coherent fascia when compared with the control tissue measured in terms of mechanical breaking strength. This new animal model employed myofascial closing after a full thickness abdominal incision using a running suture with fast-absorbable suture material. This technique produced a weak myofascial layer compared with the control tissue measured in terms of breaking strength after both 7 and 28 days. CONCLUSION: It was possible to create a healed but weak abdominal fascia in rats with a minimum of defects after incision using a running suture technique in the fascia. In contrast to other models, regular tissue defects were absent, and the model can therefore be used to evaluate the changes, both histological and mechanical, in the actively healing fascia, which may lead to incisional herniation. Furthermore, the model may also be used to study interventions performed to promote healing. This contrasts with existing models with regular fascia defects, which are not well suited for this purpose.

Hyperbilirubinemia as a predictor for appendiceal perforation: a systematic review.

BACKGROUND AND AIMS: Delayed or wrong diagnosis in patients with appendicitis can result in perforation and consequently increased morbidity and mortality. Serum bilirubin may be a useful marker for appendiceal perforation. The purpose of this systematic review was to evaluate studies investigating elevated serum bilirubin as a predictor for appendiceal perforation. MATERIAL AND METHODS: Medline, Embase, and Cochrane databases were searched for studies evaluating elevated bilirubin in the diagnosis of perforated appendicitis. Study selection criteria included English language papers evaluating serum bilirubin as a marker of appendiceal perforation in humans. A total of 189 abstracts were screened for eligibility, of which five clinical studies were included in this study. RESULTS: Bilirubin was significantly higher in patients with appendiceal perforation compared with patients with appendicitis without perforation. Elevated serum bilirubin had a sensitivity ranging from 0.38 to 0.77 and a specificity ranging from 0.70 to 0.87 in predicting appendiceal perforation. CONCLUSIONS: Elevated serum bilirubin for determining the risk of perforation in appendicitis has low sensitivity but higher specificity. This measure can therefore be used as a supplement in the diagnostic process.

Topical treatment with diclofenac, calcipotriol (vitamin-D3 analog) and difluoromethylornithine (DFMO) does not prevent nonmelanoma skin cancer in mice.

Nonmelanoma skin cancer is a common cancer type with increasing incidence. The purpose of this study was to evaluate topical application of diclofenac, calcipotriol, and difluoromethylornithine as chemoprevention in a mouse model of ultraviolet light-induced skin tumors, since these agents have been reported to have tumor inhibiting properties. One hundred twenty eight mice were treated with UVB radiation followed by chemoprevention or placebo. There were no significant effects of the treatments with respect to presence of skin tumors, number of tumors, tumor size, or survival. The investigated drugs were ineffective as chemoprevention in the dose regimens used in this study.

The inheritance of groin hernia: a systematic review.

BACKGROUND: Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias. METHODS: A literature search in the MEDLINE and Embase databases was performed with the following search terms: genetics, heredity, multifactorial inheritance, inheritance patterns, sibling relations, family relations, and abdominal hernia. Only English human clinical or register-based studies describing the inheritance of groin hernias, family history of groin hernias, or familial accumulation of groin hernias were included. RESULTS: Eleven studies evaluating 37,166 persons were included. The overall findings were that a family history of inguinal hernia was a significant risk factor for the development of a primary hernia. A family history of inguinal hernia showed a tendency toward increased hernia recurrence rate and significantly earlier recurrence. The included studies did not agree on the possible inheritance patterns differing between polygenic inheritance, autosomal dominant inheritance, and multifactorial inheritance. Furthermore, the studies did not agree on the degree of penetrance. CONCLUSION: The literature on the inheritance of groin hernias indicates that groin hernia is most likely an inherited disease; however, neither the extent of familial accumulation nor a clear inheritance pattern has yet been found. In order to establish whether groin hernias are accumulated in certain families and to what extent, large register studies based on hernia repair data or clinical examinations are needed. Groin hernia repair (inguinal and femoral hernia) is among the most commonly performed gastrointestinal surgical procedures [1]. Emergency groin hernia surgery is associated with increased mortality, increased patient-related morbidity, and increased hospital stay compared with elective groin hernia procedures [2, 3]. Identifying patients at high risk of developing groin hernia would therefore provide the possibility of timely elective surgical intervention, thus reducing the rate of emergency procedures. It could also potentially make way for individualized surgical methods in the future.

An animal model to train Lichtenstein inguinal hernia repair.

PURPOSE: Inguinal hernia repair is a common surgical procedure, and the majority of operations worldwide are performed ad modum Lichtenstein (open tension-free mesh repair). Until now, no suitable surgical training model has been available for this procedure. We propose an experimental surgical training model for Lichtenstein's procedure on the male and female pig. METHODS: In the pig, an incision is made 1 cm cranially to the inguinal sulcus where a string of subcutaneous lymph nodes is located and extends toward the pubic tubercle. The spermatic cord is located in a narrow sulcus in the pig, thus complicating the procedure if operation should be done in the inguinal canal. The chain of lymph nodes resembles the human spermatic cord and can be used to perform Lichtenstein's hernia repair. RESULTS: This experimental surgical model has been tested on two adult male pigs and three adult female pigs, and a total of 55 surgeons have been educated to perform Lichtenstein's hernia repair in these animals. CONCLUSIONS: This new experimental surgical model for training Lichtenstein's hernia repair mimics the human inguinal anatomy enough to make it suitable as a training model. The operation facilitates the training in the positioning and fixation of the mesh and can be performed numerous times on the same pig. It is therefore a useful training method for inexperienced surgeons to obtain experience in aspects of the Lichtenstein procedure.

Choosing the best animal species to mimic clinical colon anastomotic leakage in humans: a qualitative systematic review.

BACKGROUND/AIMS: Animal models are valuable for studying pathogenic factors and preventive measures for colon anastomotic leakage. The suitability of the species as models varies greatly; however, no consensus exists on which species to use. The aim of this review was to evaluate different experimental animals for the study of clinical colon anastomotic leakage. METHODS: PubMed and REX database were searched up to October 2010 to identify studies evaluating clinical colon anastomotic leakage in animal models and textbooks on experimental animals, respectively. RESULTS: Functional models of clinical colon anastomotic leakage have been developed in the mouse, pig, rat, dog and rabbit. However, extreme interventions are needed in order to produce clinical leakage in the rat. CONCLUSION: Despite the wide use of the rat in this field of research, it seems that its resistance to intra-abdominal infection makes clinical leakage difficult to produce thus rendering the rat unsuited as a model. On the basis of the available literature, we recommend using mice as models mimicking clinical colon anastomotic leakage. Pigs may be an alternative; however, the existing models in this animal are less validated and clinically relevant.

A clinical evaluation of endoscopically placed self-expanding metallic stents in patients with acute large bowel obstruction.

BACKGROUND AND AIMS: Self-expanding metallic stents (SEMS) have since 1991 established themselves as an option in the treatment of large bowel obstruction. The aim of this study was to evaluate the use of SEMS in management of acute colorectal obstructions at a Danish Surgical Gastroenterology center. MATERIAL AND METHODS: Retrospective review of charts from all patients who, in the period Marts 2002 to December 2007 underwent insertion of a SEMS for an acute large bowel obstruction. RESULTS: Of 45 patients included, SEMS was intended as a bridge to surgery in 20 patients and as palliation in 25 patients. For malignant etiology, the SEMS procedure was a technical and clinical success in 97.4% of the cases. Complications occurred in 21%, mortality rate 2,6%. For benign etiology, the SEMS procedure was a technical success in 85.7%, and a clinical success in 71.4%. Complications occurred in 71.4% of the benign cases with a mortality rate of 28,6%. CONCLUSIONS: Placement of SEMS for acute large bowel obstruction with malignant etiology is an effective and safe procedure with low mortality and morbidity. However results for benign obstructions are questionable and more research is needed to determine the role of SEMS.