Oncological Safety and Potential Cost Savings of Routine vs Selective Histopathological Examination After Appendectomy: Results of the Multicenter, Prospective, Cross-Sectional FANCY Study.

OBJECTIVE: To investigate the oncological safety and potential cost savings of selective histopathological examination after appendectomy. BACKGROUND: The necessity of routine histopathological examination after appendectomy has been questioned, but prospective studies investigating the safety of a selective policy are lacking. METHODS: In this multicenter, prospective, cross-sectional study, inspection and palpation of the (meso)appendix was performed by the surgeon in patients with suspected appendicitis. The surgeon's opinion on additional value of histopathological examination was reported before sending all specimens to the pathologist. Main outcomes were the number of hypothetically missed appendiceal neoplasms with clinical consequences benefiting the patient (upper limit two-sided 95% confidence interval below 3:1000 considered oncologically safe) and potential cost savings after selective histopathological examination. RESULTS: Seven thousand three hundred thirty-nine patients were included. After a selective policy, 4966/7339 (67.7%) specimens would have been refrained from histopathological examination. Appendiceal neoplasms with clinical consequences would have been missed in 22/4966 patients. In 5/22, residual disease was completely resected during additional surgery. Hence, an appendiceal neoplasm with clinical consequences benefiting the patient would have been missed in 1.01:1000 patients (upper limit 95% confidence interval 1.61:1000). In contrast, twice as many patients (10/22) would not have been exposed to potential harm due to re-resections without clear benefit, whereas consequences were neither beneficial nor harmful in the remaining seven. Estimated cost savings established by replacing routine for selective histopathological examination were €725,400 per 10,000 patients. CONCLUSIONS: Selective histopathological examination after appendectomy for suspected appendicitis is oncologically safe and will likely result in a reduction of pathologists' workload, less costs, and fewer re-resections without clear benefit.

Safety and economic analysis of selective histopathology following cholecystectomy: multicentre, prospective, cross-sectional FANCY study.

BACKGROUND: There is ongoing debate concerning the necessity of routine histopathological examination following cholecystectomy. In order to reduce the pathology workload and save costs, a selective approach has been suggested, but evidence regarding its oncological safety is lacking. METHODS: In this multicentre, prospective, cross-sectional study, all gallbladders removed for gallstone disease or cholecystitis were systematically examined by the surgeon for macroscopic abnormalities indicative of malignancy. Before sending all specimens to the pathologist, the surgeon judged whether histopathological examination was indicated. The main outcomes were the number of patients with hypothetically missed malignancy with clinical consequences (upper limit two-sided 95 per cent c.i. below 3:1000 considered oncologically safe) and potential cost savings of selective histopathological examination. RESULTS: Twenty-two (2.19:1000) of 10 041 specimens exhibited malignancy with clinical consequences. In case of a selective policy, surgeons would have held back 7846 of 10041 (78.1 per cent) gallbladders from histopathological examination. Malignancy with clinical consequences would have been missed in seven of 7846 patients (0.89:1000, upper limit 95% c.i. 1.40:1000). No patient benefitted from the clinical consequences, while two were harmed (futile additional surgery). Of 15 patients in whom malignancy with clinical consequences would have been diagnosed, one benefitted (residual disease radically removed), two potentially benefitted (palliative systemic therapy), and four experienced harm (futile additional surgery). Estimated cost savings established by replacing routine for selective histopathological examination were €703 500 per 10 000 patients. CONCLUSION: Selective histopathological examination following cholecystectomy is oncologically safe and could reduce pathology workload, costs, and futile re-resections.

Safety and cost analysis of selective histopathological examination following appendicectomy and cholecystectomy (FANCY study): protocol and statistical analysis plan of a prospective observational multicentre study.

INTRODUCTION: Routine histopathological examination following appendicectomy and cholecystectomy has significant financial implications and comprises a substantial portion of the pathologists' workload, while the incidence of unexpected pathology is low. The aim of the selective histopathological examination Following AppeNdicectomy and CholecystectomY (FANCY) study is to investigate the oncological safety and potential cost savings of selective histopathological examination based on macroscopic assessment performed by the surgeon. METHODS AND ANALYSIS: This is a Dutch multicentre prospective observational study, in which removed appendices and gallbladders will be systematically assessed by the operating surgeon for macroscopic abnormalities suspicious for malignant neoplasms. After visual inspection and digital palpation of the removed specimen, the operating surgeon will report whether macroscopic abnormalities suspicious for a malignant neoplasm are present, and if he or she believes additional microscopic examination by the pathologist is indicated. Regardless of the surgeon's assessment, all specimens will be sent for histopathological examination. In this way, routine histopathological examination can be compared with a hypothetical situation in which specimens are routinely examined by surgeons and only sent to the pathologist on indication. The two main outcomes are oncological safety and potential cost savings of a selective policy. Oncological safety of selective histopathological examination will be assessed by calculating the number of patients in whom a histopathological diagnosis of an appendiceal neoplasm or gallbladder cancer with clinical consequences benefitting the patient would have been missed. A cost analysis will be performed to quantify the potential cost savings. ETHICS AND DISSEMINATION: The study protocol was reviewed by the Institutional Review Board of the Amsterdam UMC, location AMC, which decided that the Dutch Medical Research Involving Human Subjects Act is not applicable. In all participating centres, approval for execution of the FANCY study has been obtained from the local Institutional Review Board before the start of inclusion of patients. The study results will be disseminated through peer-reviewed publications and conference presentations. Guidelines will be revised according to the findings of the study. TRIAL REGISTRATION NUMBER: NCT03510923.

Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial.

BACKGROUND: Previous studies have suggested that sigmoidectomy with primary anastomosis is superior to Hartmann's procedure. The likelihood of stoma reversal after primary anastomosis has been reported to be higher and reversal seems to be associated with lower morbidity and mortality. Although promising, results from these previous studies remain uncertain because of potential selection bias. Therefore, this study aimed to assess outcomes after Hartmann's procedure versus sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy, for perforated diverticulitis with purulent or faecal peritonitis (Hinchey III or IV disease) in a randomised trial. METHODS: A multicentre, randomised, open-label, superiority trial was done in eight academic hospitals and 34 teaching hospitals in Belgium, Italy, and the Netherlands. Patients aged between 18 and 85 years who presented with clinical signs of general peritonitis and suspected perforated diverticulitis were eligible for inclusion if plain abdominal radiography or CT scan showed diffuse free air or fluid. Patients with Hinchey I or II diverticulitis were not eligible for inclusion. Patients were allocated (1:1) to Hartmann's procedure or sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy. Patients were enrolled by the surgeon or surgical resident involved, and secure online randomisation software was used in the operating room or by the trial coordinator on the phone. Random and concealed block sizes of two, four, or six were used, and randomisation was stratified by age (<60 and ≥60 years). The primary endpoint was 12-month stoma-free survival. Patients were analysed according to a modified intention-to-treat principle. The trial is registered with the Netherlands Trial Register, number NTR2037, and ClinicalTrials.gov, number NCT01317485. FINDINGS: Between July 1, 2010, and Feb 22, 2013, and June 9, 2013, and trial termination on June 3, 2016, 133 patients (93 with Hinchey III disease and 40 with Hinchey IV disease) were randomly assigned to Hartmann's procedure (68 patients) or primary anastomosis (65 patients). Two patients in the Hartmann's group were excluded, as was one in the primary anastomosis group; the modified intention-to-treat population therefore consisted of 66 patients in the Hartmann's procedure group (46 with Hinchey III disease, 20 with Hinchey IV disease) and 64 in the primary anastomosis group (46 with Hinchey III disease, 18 with Hinchey IV disease). In 17 (27%) of 64 patients assigned to primary anastomosis, no stoma was constructed. 12-month stoma-free survival was significantly better for patients undergoing primary anastomosis compared with Hartmann's procedure (94·6% [95% CI 88·7-100] vs 71·7% [95% CI 60·1-83·3], hazard ratio 2·79 [95% CI 1·86-4·18]; log-rank p<0·0001). There were no significant differences in short-term morbidity and mortality after the index procedure for Hartmann's procedure compared with primary anastomosis (morbidity: 29 [44%] of 66 patients vs 25 [39%] of 64, p=0·60; mortality: two [3%] vs four [6%], p=0·44). INTERPRETATION: In haemodynamically stable, immunocompetent patients younger than 85 years, primary anastomosis is preferable to Hartmann's procedure as a treatment for perforated diverticulitis (Hinchey III or Hinchey IV disease). FUNDING: Netherlands Organisation for Health Research and Development.

Trocar types in laparoscopy.

BACKGROUND: Laparoscopic surgery has led to great clinical improvements in many fields of surgery; however, it requires the use of trocars, which may lead to complications as well as postoperative pain. The complications include intra-abdominal vascular and visceral injury, trocar site bleeding, herniation and infection. Many of these are extremely rare, such as vascular and visceral injury, but may be life-threatening; therefore, it is important to determine how these types of complications may be prevented. It is hypothesised that trocar-related complications and pain may be attributable to certain types of trocars. This systematic review was designed to improve patient safety by determining which, if any, specific trocar types are less likely to result in complications and postoperative pain. OBJECTIVES: To analyse the rates of trocar-related complications and postoperative pain for different trocar types used in people undergoing laparoscopy, regardless of the condition. SEARCH METHODS: Two experienced librarians conducted a comprehensive search for randomised controlled trials (RCTs) in the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, CDSR and DARE (up to 26 May 2015). We checked trial registers and reference lists from trial and review articles, and approached content experts. SELECTION CRITERIA: RCTs that compared rates of trocar-related complications and postoperative pain for different trocar types used in people undergoing laparoscopy. The primary outcomes were major trocar-related complications, such as mortality, conversion due to any trocar-related adverse event, visceral injury, vascular injury and other injuries that required intensive care unit (ICU) management or a subsequent surgical, endoscopic or radiological intervention. Secondary outcomes were minor trocar-related complications and postoperative pain. We excluded trials that studied non-conventional laparoscopic incisions. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted the study selection, risk of bias assessment and data extraction. We used GRADE to assess the overall quality of the evidence. We performed sensitivity analyses and investigation of heterogeneity, where possible. MAIN RESULTS: We included seven RCTs (654 participants). One RCT studied four different trocar types, while the remaining six RCTs studied two different types. The following trocar types were examined: radially expanding versus cutting (six studies; 604 participants), conical blunt-tipped versus cutting (two studies; 72 participants), radially expanding versus conical blunt-tipped (one study; 28 participants) and single-bladed versus pyramidal-bladed (one study; 28 participants). The evidence was very low quality: limitations were insufficient power, very serious imprecision and incomplete outcome data. Primary outcomesFour of the included studies reported on visceral and vascular injury (571 participants), which are two of our primary outcomes. These RCTs examined 473 participants where radially expanding versus cutting trocars were used. We found no evidence of a difference in the incidence of visceral (Peto odds ratio (OR) 0.95, 95% confidence interval (CI) 0.06 to 15.32) and vascular injury (Peto OR 0.14, 95% CI 0.0 to 7.16), both very low quality evidence. However, the incidence of these types of injuries were extremely low (i.e. two cases of visceral and one case of vascular injury for all of the included studies). There were no cases of either visceral or vascular injury for any of the other trocar type comparisons. No studies reported on any other primary outcomes, such as mortality, conversion to laparotomy, intensive care admission or any re-intervention. Secondary outcomesFor trocar site bleeding, the use of radially expanding trocars was associated with a lower risk of trocar site bleeding compared to cutting trocars (Peto OR 0.28, 95% CI 0.14 to 0.54, five studies, 553 participants, very low quality evidence). This suggests that if the risk of trocar site bleeding with the use of cutting trocars is assumed to be 11.5%, the risk with the use of radially expanding trocars would be 3.5%. There was insufficient evidence to reach a conclusion regarding other trocar types, their related complications and postoperative pain, as no studies reported data suitable for analysis. AUTHORS' CONCLUSIONS: Data were lacking on the incidence of major trocar-related complications, such as visceral or vascular injury, when comparing different trocar types with one another. However, caution is urged when interpreting these results because the incidence of serious complications following the use of a trocar was extremely low. There was very low quality evidence for minor trocar-related complications suggesting that the use of radially expanding trocars compared to cutting trocars leads to reduced incidence of trocar site bleeding. These secondary outcomes are viewed to be of less clinical importance.Large, well-conducted observational studies are necessary to answer the questions addressed in this review because serious complications, such as visceral or vascular injury, are extremely rare. However, for other outcomes, such as trocar site herniation, bleeding or infection, large observational studies may be needed as well. In order to answer these questions, it is advisable to establish an international network for recording these types of complications following laparoscopic surgery.

Laparoscopic peritoneal lavage or sigmoidectomy for perforated diverticulitis with purulent peritonitis: a multicentre, parallel-group, randomised, open-label trial.

BACKGROUND: Case series suggest that laparoscopic peritoneal lavage might be a promising alternative to sigmoidectomy in patients with perforated diverticulitis. We aimed to assess the superiority of laparoscopic lavage compared with sigmoidectomy in patients with purulent perforated diverticulitis, with respect to overall long-term morbidity and mortality. METHODS: We did a multicentre, parallel-group, randomised, open-label trial in 34 teaching hospitals and eight academic hospitals in Belgium, Italy, and the Netherlands (the Ladies trial). The Ladies trial is split into two groups: the LOLA group comparing laparoscopic lavage with sigmoidectomy and the DIVA group comparing Hartmann's procedure with sigmoidectomy plus primary anastomosis. The DIVA section of this trial is still underway but here we report the results of the LOLA section. Patients with purulent perforated diverticulitis were enrolled for LOLA, excluding patients with faecal peritonitis, aged older than 85 years, with high-dose steroid use (≥20 mg daily), and haemodynamic instability. Patients were randomly assigned (2:1:1; stratified by age [<60 years vs ≥60 years]) using secure online computer randomisation to laparoscopic lavage, Hartmann's procedure, or primary anastomosis in a parallel design after diagnostic laparoscopy. Patients were analysed according to a modified intention-to-treat principle and were followed up after the index operation at least once in the outpatient setting and after sigmoidoscopy and stoma reversal, according to local protocols. The primary endpoint was a composite endpoint of major morbidity and mortality within 12 months. This trial is registered with ClinicalTrials.gov, number NCT01317485. FINDINGS: Between July 1, 2010, and Feb 22, 2013, 90 patients were randomly assigned in the LOLA section of the Ladies trial when the study was terminated by the data and safety monitoring board because of an increased event rate in the lavage group. Two patients were excluded for protocol violations. The primary endpoint occurred in 30 (67%) of 45 patients in the lavage group and 25 (60%) of 42 patients in the sigmoidectomy group (odds ratio 1·28, 95% CI 0·54-3·03, p=0·58). By 12 months, four patients had died after lavage and six patients had died after sigmoidectomy (p=0·43). INTERPRETATION: Laparoscopic lavage is not superior to sigmoidectomy for the treatment of purulent perforated diverticulitis. FUNDING: Netherlands Organisation for Health Research and Development.

Endostapler or endoloops for securing the appendiceal stump in laparoscopic appendectomy: a retrospective cohort study.

BACKGROUND: Laparoscopic appendectomy is the treatment of choice for appendicitis provided sufficient laparoscopic expertise is available. The endostapler possibly provides an easier and safer closure of the appendiceal stump, but at greater expense. This study aimed to compare two strategies for closure of the appendiceal stump in a large retrospective cohort of patients. METHODS: This study reviewed patients who underwent laparoscopic appendectomy for acute appendicitis in three academic hospitals and two regional hospitals in The Netherlands during the period 1 January 2007 to 30 June 2011. The endostapler was routinely used in two hospitals and selectively used in the remaining three hospitals. Both strategies were compared for complications according to the Clavien-Dindo classification. RESULTS: A total of 1,036 patients were analyzed according to the strategy followed. The 571 patients in the first group were routinely treated with the endostapler. For the 465 patients in the second group, the intentional method of stump closure was with endoloops. The endostapler was used when indicated for 69 of these patients. The patient characteristics did not differ between the two groups. The groups also did not differ significantly in number of intra- and postoperative complications. In both groups, 4.3 % of the patients had complications classified as grade 3 or higher. There were no significant differences in the prevalence of intraabdominal abscesses (3.2 % vs. 4.3) or wound infections (0.4 and 1.5 %). In a multivariate analysis, the chosen strategy for stump closure was not a significant predictor for postoperative complications. CONCLUSION: Routine use of the endostapler showed no clinical advantages over the use of endoloops with selective endostapler closure. The latter strategy is preferable because it is more cost effective.

Routine histopathology for carcinoma in cholecystectomy specimens not evidence based: a systematic review.

BACKGROUND: Routine histopathological examination of gallbladder specimens is mainly performed to identify unexpected gallbladder carcinoma (GBC). This systematic review assesses the prevalence and characteristics of GBC in cholecystectomy specimens. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for all articles reporting on the finding of GBC in cholecystectomy specimens. RESULTS: Of the 30 articles included, 20 were from Europe and the United States, and 10 were of Asian origin. In the Western studies, 276 cases of GBC were found in 61,542 specimens (median prevalence 0.4%, 95% confidence interval [CI] 0.3-0.6). Of these, 65% were expected pre- or intraoperatively. In the Asian studies, 344 cases of GBC were found in 37,365 specimens (median prevalence 1.2%, 95% CI 0.8-1.7). Of these, 45% were expected pre- or intraoperatively. In a subgroup analysis, identification of previously unexpected GBC affected treatment in only a minority of patients. In total, 72% of the patients received no further treatment and 32 patients (22%) received secondary surgery, of whom 15 patients survived at least 1 year. CONCLUSIONS: The histopathological finding of GBC after cholecystectomy appears to be a rare event. The prevalence of unexpected GBC was higher in Asian studies than in Western studies. The pre- and intraoperative sensitivity for this carcinoma is low. Moreover, the diagnosis of GBC at the time of histopathology is usually inconsequential. The results of this systematic review do not support routine histopathology of cholecystectomy specimens in clinical practice.

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitis and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitis in perforated diverticulitis (NTR2037).

BACKGROUND: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). METHODS/DESIGN: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs. DISCUSSION: The Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis. TRIAL REGISTRATION: Nederlands Trial Register NTR2037.

[Treatment for diverticulitis not thoroughly researched]. / Geen goed onderzochte behandeling voor diverticulitis.

In the Netherlands approximately 14,000 patients are referred to hospital for diverticular disease each year. Overall controversy persists about four aspects of treatment of the different stages of diverticulitis, i.e. the role of antibiotics in the treatment of mild diverticulitis, the question of whether elective surgical resection is justified in recurrent diverticulitis or in persisting abdominal symptoms after an episode of diverticulitis, the question of whether patients with purulent peritonitis due to perforation may be treated with laparoscopic peritoneal lavage instead of Hartmann's procedure, and finally, whether resection with a primary anastomosis is a feasible and safe alternative to Hartmann's procedure in the surgical treatment of Hinchey III or IV diverticulitis. These questions will be addressed in four upcoming Dutch randomised trials.