Primary Open Versus Closed Implantation Strategy for Totally Implantable Venous Access Ports: The Multicentre Randomized Controlled PORTAS-3 Trial (DRKS 00004900).

OBJECTIVES: PORTAS-3 was designed to compare the frequency of pneumothorax or haemothorax in a primary open versus closed strategy for port implantation. BACKGROUND DATA: The implantation strategy for totally implantable venous access ports with the optimal benefit/risk ratio remains unclear. METHODS: PORTAS-3 was a multicentre, randomized, controlled, parallel-group superiority trial. Adult patients with oncological disease scheduled for elective port implantation were randomized to a primary open or closed strategy. Primary endpoint was the rate of pneumothorax or haemothorax. Assuming a difference of 2.5% between the 2 groups, a sample size of 1154 patients was needed to prove superiority of the open group. A logistic regression model after the intention-to-treat principle was applied for analysis of the primary endpoint. RESULTS: Between November 9, 2014 and September 5, 2016, 1205 patients were randomized. Of these, 1159 (open n = 583; closed n = 576) were finally analyzed. The rate of pneumothorax or haemothorax was significantly reduced with the open strategy [odds ratio 0.27, 95% confidence interval (CI) 0.09-0.88; P = 0.029]. Operation time was shorter for the closed strategy. Primary success rates, tolerability, morbidity, dose rate of radiation, and 30-day mortality did not differ significantly between the groups. CONCLUSION: A primary open strategy by cut-down of the cephalic vein, if necessary enhanced by a modified Seldinger technique, reduces the frequency of pneumothorax or haemothorax after central venous port implantation significantly compared with a closed strategy by primary puncture of the subclavian vein without routine sonographic guidance. Therefore, open surgical cut-down should be the reference standard for port implantation in comparable cohorts. TRIAL REGISTRATION: German Clinical Trials Register DRKS 00004900.

Total Parathyroidectomy With Routine Thymectomy and Autotransplantation Versus Total Parathyroidectomy Alone for Secondary Hyperparathyroidism: Results of a Nonconfirmatory Multicenter Prospective Randomized Controlled Pilot Trial.

OBJECTIVE: This randomized controlled multicenter pilot trial was conducted to find robust estimates for the rates of recurrence of 2 surgical strategies for secondary hyperparathyroidism (SHPT) within 36 months of follow-up. BACKGROUND: SHPT is a frequent consequence of chronic renal failure. Total parathyroidectomy with autotransplantation (TPTX+AT) and subtotal parathyroidectomy (SPTX) are the standard surgical procedures. Total parathyroidectomy alone (TPTX) might be a good alternative, as morbidity and recurrence rates are low according to small-scale retrospective studies. METHODS: The trial was performed as a nonconfirmatory randomized controlled pilot trial with 100 patients on long-term dialysis with otherwise uncontrollable SHPT to generate data on the rate of recurrent disease within a 3-year follow-up period after TPTX or TPTX+AT. Parathyroid hormone (PTH) and calcium levels, recurrent or persistent hyperparathyroidism, parathyroid reoperations, morbidity, and mortality were evaluated during a 3-year follow-up. RESULTS: A total of 52 patients underwent TPTX and 48 TPTX+AT. Patient characteristics, preoperative baseline data, duration of surgery (02:29 vs 02:47 hrs, P = 0.17) and mean hospital stay (10 ± 7.1 vs 8 ± 3.7 days, P = 0.11) did not differ significantly. Persistent SHPT developed in 1 TPTX and 2 TPTX+AT patients. None of the TPTX patients required delayed parathyroid AT to treat permanent hypoparathyroidism. Serum-calcium values were similar (2.1 ± 0.3 vs 2.1 ± 0.2, P = 0.95) whereas PTH rose by time in the TPTX+AT group and was significantly higher at the end of follow-up when compared with the TPTX group (31.7 ± 43.6 vs 98.2 ± 156.8, P = 0.02). Recurrent SHPT developed in 4 TPTX+AT and none of the TPTX patients. CONCLUSIONS: TPTX+AT and TPTX seem to be safe and equally effective for the treatment of otherwise uncontrollable SHPT. TPTX seems to suppress PTH more effectively and showed no recurrences after 3 years. The hypothesis that TPTX is superior to TPTX+AT referring to the rate of recurrent SHPT has to be tested in a large-scale confirmatory trial. Nevertheless, TPTX seems to be a feasible alternative therapeutic option for the surgical treatment of SHPT.

Incisional Hernia Rates After Laparoscopic or Open Abdominal Surgery-A Systematic Review and Meta-Analysis.

BACKGROUND: Incisional hernias are one of the most common long-term complications associated with open abdominal surgery. The aim of this review and meta-analysis was to systematically assess laparoscopic versus open abdominal surgery as a general surgical strategy in all available indications in terms of incisional hernia occurrence. METHODS: A systematic literature search was performed to identify randomized controlled trials comparing incisional hernia rates after laparoscopic versus open abdominal surgery in all indications. Random effects meta-analyses were calculated and presented as risk differences (RD) with their corresponding 95 % confidence intervals (CI). RESULTS: 24 trials (3490 patients) were included. Incisional hernias were significantly reduced in the laparoscopic group (RD -0.06, 95 % CI [-0.09, -0.03], p = 0.0002, I (2) = 75). The advantage of the laparoscopic procedure persisted in the subgroup of total-laparoscopic interventions (RD -0.14, 95 % CI [-0.22, -0.06], p = 0.001, I (2) = 87 %), whereas laparoscopically assisted procedures did not show a significant reduction of incisional hernias compared to open surgery (RD -0.01, 95 % CI [-0.03, 0.01], p = 0.31, I (2) = 35 %). Wound infections were significantly reduced in the laparoscopic group (RD -0.06, 95 % CI [-0.09, -0.03], p < 0.0001, I (2) = 35 %); overall postoperative morbidity was comparable in both groups (RD -0.06, 95 % CI [-0.13, 0.00], p = 0.06; I (2) = 64 %). Open abdominal surgery showed a significantly longer hospital stay compared to laparoscopy (RD -1.92, 95 % CI [-2.67, -1.17], p < 0.00001, I (2) = 87 %). At short-term follow-up, quality of life was in favor of laparoscopy. CONCLUSIONS: Incisional hernias are less frequent using the total-laparoscopic approach instead of open abdominal surgery. Whenever possible, the less traumatic access should be chosen.

Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma.

BACKGROUND: Pancreatic cancer is the fourth-leading cause of cancer death for both, men and women. The standard treatment for resectable tumours consists of a classic Whipple (CW) operation or a pylorus-preserving pancreaticoduodenectomy (PPW). It is unclear which of these procedures is more favourable in terms of survival, postoperative mortality, complications, and quality of life. OBJECTIVES: The objective of this systematic review was to compare the effectiveness of CW and PPW techniques for surgical treatment of cancer of the pancreatic head and the periampullary region. SEARCH METHODS: We conducted searches on 28 March 2006, 11 January 2011, 9 January 2014, and 18 August 2015 to identify all randomised controlled trials (RCTs), while applying no language restrictions. We searched the following electronic databases on 18 August 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE) from the Cochrane Library (2015, Issue 8); MEDLINE (1946 to August 2015); and EMBASE (1980 to August 2015). We also searched abstracts from Digestive Disease Week and United European Gastroenterology Week (1995 to 2010); we did not update this part of the search for the 2014 and 2015 updates because the prior searches did not contribute any additional information. We identified two additional trials through the updated search in 2015. SELECTION CRITERIA: RCTs comparing CW versus PPW including participants with periampullary or pancreatic carcinoma. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials. We used a random-effects model for pooling data. We compared binary outcomes using odds ratios (ORs), pooled continuous outcomes using mean differences (MDs), and used hazard ratios (HRs) for meta-analysis of survival. Two review authors independently evaluated the methodological quality and risk of bias of included trials according to the standards of The Cochrane Collaboration. MAIN RESULTS: We included eight RCTs with a total of 512 participants. Our critical appraisal revealed vast heterogeneity with respect to methodological quality and outcome parameters. Postoperative mortality (OR 0.64, 95% confidence interval (CI) 0.26 to 1.54; P = 0.32), overall survival (HR 0.84, 95% CI 0.61 to 1.16; P = 0.29), and morbidity showed no significant differences, except of delayed gastric emptying, which significantly favoured CW (OR 3.03, 95% CI 1.05 to 8.70; P = 0.04). Furthermore, we noted that operating time (MD -45.22 minutes, 95% CI -74.67 to -15.78; P = 0.003), intraoperative blood loss (MD -0.32 L, 95% CI -0.62 to -0.03; P = 0.03), and red blood cell transfusion (MD -0.47 units, 95% CI -0.86 to -0.07; P = 0.02) were significantly reduced in the PPW group. All significant results were associated with low-quality evidence based on GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. AUTHORS' CONCLUSIONS: Current evidence suggests no relevant differences in mortality, morbidity, and survival between the two operations. However, some perioperative outcome measures significantly favour the PPW procedure. Given obvious clinical and methodological heterogeneity, future high-quality RCTs of complex surgical interventions based on well-defined outcome parameters are required.

Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma.

Background Pancreatic cancer is the fourth leading cause of cancer death for men and the fifth for women. The standard treatment for resectable tumours consists of a classic Whipple (CW) operation or a pylorus-preserving pancreaticoduodenectomy (PPW). It is unclear which of these procedures is more favourable in terms of survival, mortality, complications and quality of life.Objectives The objective of this systematic review is to compare the effectiveness of CW and PPW techniques for surgical treatment of cancer of the pancreatic head and the periampullary region.Search methods We conducted searches on 28 March 2006, 11 January 2011 and 9 January 2014 to identify all randomised controlled trials (RCTs),while applying no language restrictions. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects(DARE) from The Cochrane Library (2013, Issue 4); MEDLINE (1946 to January 2014); and EMBASE (1980 to January 2014). We also searched abstracts from Digestive Disease Week and United European Gastroenterology Week (1995 to 2010). We identified no additional studies upon updating the systematic review in 2014.Selection criteria We considered RCTs comparing CW versus PPW to be eligible if they included study participants with periampullary or pancreatic carcinoma. Data collection and analysis Two review authors independently extracted data from the included studies. We used a random-effects model for pooling data. We compared binary outcomes using odds ratios (ORs), pooled continuous outcomes using mean differences (MDs) and used hazard ratios (HRs) for meta-analysis of survival. Two review authors independently evaluated the methodological quality and risk of bias of included studies according to the standards of The Cochrane Collaboration.Main results We included six RCTs with a total of 465 participants. Our critical appraisal revealed vast heterogeneity with respect to methodological quality and outcome parameters. In-hospital mortality (OR 0.49, 95% confidence interval (CI) 0.17 to 1.40; P value 0.18), overall survival (HR 0.84, 95% CI 0.61 to 1.16; P value 0.29) and morbidity showed no significant differences. However, we noted that operating time (MD -68.26 minutes, 95% CI -105.70 to -30.83; P value 0.0004) and intraoperative blood loss (MD -0.76 mL, 95%CI -0.96 to -0.56; P value < 0.00001) were significantly reduced in the PPW group. All significant results are associated with low quality of evidence as determined on the basis of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria.Authors' conclusions No evidence suggests relevant differences in mortality, morbidity and survival between the two operations. Given obvious clinical and methodological heterogeneity, future research must be undertaken to perform high-quality randomised controlled trials of complex surgical interventions on the basis of well-defined outcome parameters.

Effectiveness of triclosan-coated PDS Plus versus uncoated PDS II sutures for prevention of surgical site infection after abdominal wall closure: the randomised controlled PROUD trial.

BACKGROUND: Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery, and triclosan-coated sutures were developed to reduce their occurrence. The aim of the PROUD trial was to obtain reliable data for the effectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure, compared with non-coated PDS II sutures, in the prevention of surgical site infections. METHODS: This multicentre, randomised controlled group-sequential superiority trial was done in 24 German hospitals. Adult patients (aged ≥18 years) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion. Exclusion criteria were impaired mental state, language problems, and participation in another intervention trial that interfered with the intervention or outcome of this trial. A central web-based randomisation tool was used to randomly assign eligible participants by permuted block randomisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures (PDS Plus) or uncoated sutures (PDS II) for abdominal fascia closure. The primary endpoint was the occurrence of superficial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation. Patients, surgeons, and the outcome assessors were masked to group assignment. Interim and final analyses were by modified intention to treat. This trial is registered with the German Clinical Trials Register, number DRKS00000390. FINDINGS: Between April 7, 2010, and Oct 19, 2012, 1224 patients were randomly assigned to intervention groups (607 to PDS Plus, and 617 to PDS II), of whom 1185 (587 PDS Plus and 598 PDS II) were analysed by intention to treat. The study groups were well balanced in terms of patient and procedure characteristics. The occurrence of surgical site infections did not differ between the PDS Plus group (87 [14·8%] of 587) and the PDS II group (96 [16·1%] of 598; OR 0·91, 95% CI 0·66-1·25; p=0·64). Serious adverse events also did not differ between the groups-146 of 583 (25·0%) patients treated with PDS Plus had at least one serious adverse event, compared with 138 of 602 (22·9%) patients treated with PDS II; p=0·39). INTERPRETATION: Triclosan-coated PDS Plus did not reduce the occurrence of surgical site infection after elective midline laparotomy. Innovative, multifactorial strategies need to be developed and assessed in future trials to reduce surgical site infections. FUNDING: Johnson & Johnson Medical Limited.

Laparoscopic versus conventional ileoanal pouch procedure in patients undergoing elective restorative proctocolectomy (LapConPouch Trial)-a randomized controlled trial.

PURPOSE: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical procedure for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). While minimal invasive techniques have been applied increasingly, clear evidence of superiority for laparoscopic pouch procedures is not yet available. The aim of the LapConPouch Trial was to compare the effectiveness of laparoscopic (LAP) versus conventional (CON) ileoanal pouch procedure in patients undergoing elective restorative proctocolectomy. METHODS: The trial was designed as a single-centre, pre-operatively randomized, controlled trial using a two-group parallel superiority design. Eligible for participation were patients scheduled for restorative proctocolectomy either for FAP or for UC. Patients and outcome assessors were blinded to group assignment. The primary endpoint was defined as the amount of blood loss. Statistical analyses were explorative since the trial had to be stopped prematurely. RESULTS: A total of 42 patients (21 LAP (50.0 %); 21 CON (50.0 %)) were randomized. The trial had to be stopped prematurely due to insufficient patient recruitment. There was no difference in the amount of blood loss between both groups: LAP 261.5 ± 195.4 ml, CON 228.1 ± 119.5 ml. Secondary endpoints differ in both groups. Laparoscopic surgery was superior regarding the length of skin incision; in contrast, the conventional approach was superior in duration of operation. There were no discrepancies in length of hospital stay, postoperative pain, bowel function, and quality of life between both approaches. The conversion rate from LAP to CON approach was 23.8 %. CONCLUSION: There was no difference with respect to blood loss between the LAP and the CON group. The LAP approach is feasible for restorative proctocolectomy, and IPAA seems at least as safe as CON surgery. The most obvious advantage of the minimal invasive technique is the improved cosmesis.

Comparative evaluation of nine faecal immunochemical tests for the detection of colorectal cancer.

BACKGROUND: Faecal immunochemical tests (FITs) for haemoglobin are increasingly used for non-invasive screening for colorectal cancer (CRC) but large scale comparative studies of different FITs for detection of CRC, overall and by stage, are sparse. We aimed to determine and compare performance of different FITs for the detection of CRC, and to assess their stage-specific sensitivities. MATERIAL AND METHODS: We assessed sensitivity, specificity and their corresponding 95% confidence intervals for six qualitative FITs among 74 CRC cases (59% stage I or II cancers) and 1480 controls free of colorectal neoplasm. Overall and stage-specific receiver operating characteristic curves were derived for three quantitative FITs. The areas under the curves (AUCs) were calculated and compared. RESULTS: Pairs of overall sensitivity and specificity of the qualitative FITs ranged from 66% and 96% to 92% and 62%, respectively. For the three quantitative tests, AUCs ranged from 0.90 to 0.92, with sensitivities ranging from 80% to 87% at cut-offs yielding 90% specificity. AUCs ranged from 0.85 to 0.92, 0.94 to 0.96, and 0.86 to 0.93 for stage I, stage II and advanced stages (stage III and IV) cancers, respectively. At a specificity of 90%, the tests detected 65%-85% of stage I cancers. CONCLUSION: The diagnostic performance of FITs regarding detection of CRC is promising, even though the pre-defined cut-offs of some of the qualitative FITs need to be adjusted to limit false-positive rates in screening setting. At cut-off levels yielding 90% specificity, the quantitative tests detected the vast majority of CRCs, even at early stages.

Colorectal cancers occurring after colonoscopy with polyp detection: sites of polyps and sites of cancers.

Colonoscopy with detection and removal of neoplasms strongly reduces risk of colorectal cancer (CRC). Nevertheless, CRCs occur after colonoscopic polypectomy. We assessed agreement beyond chance of location of polyps detected at colonoscopy and of subsequent CRCs to estimate the share of cancers that might be due to field effects or neoplasm recrudescence. In a population-based case-control study conducted in Germany (3,148 cases), detailed history and results of colonoscopies conducted within 10 years before cancer diagnosis were obtained by interview and from medical records. We determined the observed proportion of cancers for which a polyp had been detected at the same colorectal subsite at the preceding colonoscopy and compared it to the proportion expected by chance. A total of 155 cases with physician validated polyp detection at the preceding colonoscopy were identified. Among 148 cases with cancer restricted to a single subsite, 43 (29.1%) had a polyp detected in the same colorectal subsite at the preceding colonoscopy. Agreement of location of cancer occurrence and preceding polyp detection would have been expected by chance for 27 cases, and agreement beyond chance was estimated to account for 16 cases (10.8%, 95% confidence interval 2.7%-19.3%). Our study suggests that less than one of nine CRCs occurring within 10 years after colonoscopy with polyp detection may be due to field effects or polyp recrudescence.

DeloRes trial: study protocol for a randomized trial comparing two standardized surgical approaches in rectal prolapse - Delorme's procedure versus resection rectopexy.

BACKGROUND: More than 100 surgical approaches to treat rectal prolapse have been described. These can be done through the perineum or transabdominally. Delorme's procedure is the most frequently used perineal, resection rectopexy the most commonly used abdominal procedure. Recurrences seem more common after perineal compared to abdominal techniques, but the latter may carry a higher risk of peri- and postoperative morbidity and mortality. METHODS/DESIGN: DeloRes is a randomized, controlled, observer-blinded multicenter trial with two parallel groups. Patients with a full-thickness rectal prolapse (third degree prolapse), considered eligible for both operative methods are included. The primary outcome is time to recurrence of full-thickness rectal prolapse during the 24 months following primary surgery. Secondary endpoints are time to and incidence of recurrence of full-thickness rectal prolapse during the 5-year follow-up, duration of surgery, morbidity, hospital stay, quality of life, constipation, and fecal incontinence. A meta-analysis was done on the basis of the available data on recurrence rates from 17 publications comprising 1,140 patients. Based on the results of a meta-analysis it is assumed that the recurrence rate after 2 years is 20% for Delorme's procedure and 5% for resection rectopexy. Considering a rate of lost to follow-up without recurrence of 30% a total of 130 patients (2 x 65 patients) was calculated as an adequate sample size to assure a power of 80% for the confirmatory analysis. DISCUSSION: The DeloRes Trial will clarify which procedure results in a smaller recurrence rate but also give information on how morbidity and functional results compare. TRIAL REGISTRATION: German Clinical Trial Number DRKS00000482.

Role of colonoscopy and polyp characteristics in colorectal cancer after colonoscopic polyp detection: a population-based case-control study.

BACKGROUND: Studies have identified characteristics of adenomas detected on colonoscopy to be predictive of adenoma recurrence. OBJECTIVE: To assess the role of both colonoscopy-related factors and polyp characteristics on the risk for colorectal cancer after colonoscopic polyp detection. DESIGN: Population-based case-control study (3148 case participants and 3274 control participants). SETTING: Rhine-Neckar region of Germany. PATIENTS: Case and control participants with physician-validated detection of polyps (other than hyperplastic polyps) at a previous colonoscopy in the past 10 years. MEASUREMENTS: Detailed history and results of previous colonoscopies were obtained through interviews and medical records. Case and control participants were compared according to colonoscopy-related factors (incompleteness, poor bowel preparation, incomplete removal of all polyps, and no surveillance colonoscopy within 5 years) and polyp characteristics (≥ 1 cm, villous components or high-grade dysplasia, ≥ 3 polyps, and ≥ 1 proximal polyp). Odds ratios (ORs) and attributable fractions were derived by using multiple logistic regression and the Levin formula. RESULTS: 155 case participants and 260 control participants with physician-validated polyp detection in the past 10 years were identified. The following characteristics were significantly more common among case participants than among control participants: not all polyps completely removed (29.0% vs. 9.6%; OR, 3.73 [95% CI, 2.11 to 6.60]), no surveillance colonoscopy within 5 years (26.5% vs. 11.5%; OR, 2.96 [CI, 1.70 to 5.16]), and detection of 3 or more polyps (14.2% vs. 7.3%; OR, 2.21 [CI, 1.07 to 4.54]). Odds ratios ranged from 1.12 to 1.42 and CIs included 1.00 for all other variables. Overall, 41.1% and 21.7% of cancer cases were statistically attributable to colonoscopy-related factors and polyp characteristics, respectively. LIMITATION: This was an observational study with potential for residual confounding and selection bias. CONCLUSION: Colonoscopy-related factors are more important than polyp characteristics for stratification of colorectal cancer risk after colonoscopic polyp detection in the community setting.

Risk of colorectal cancer after detection and removal of adenomas at colonoscopy: population-based case-control study.

PURPOSE: Empirical evidence for recommendations of surveillance intervals after detection and removal of adenomas at colonoscopy is still sparse and mostly based on observations of adenoma recurrence. We aimed to assess risk of colorectal cancer (CRC) according to time since polypectomy and factors that might be relevant for risk stratification. METHODS: In a population-based case-control study conducted in Germany, detailed history and results of previous large-bowel endoscopies were obtained by interview and from medical records. Risk of CRC among participants with detection of at least one adenoma at a preceding colonoscopy compared with participants without previous large-bowel endoscopy was assessed according to time since polypectomy among 2,582 cases with CRC and 1,798 matched controls. RESULTS: Adjusted odds ratios (95% CIs) of CRC for participants with polypectomy less than 3, 3 to 5, and 6 to 10 years ago (using participants without previous endoscopy as reference group) were 0.2 (0.2 to 0.3), 0.4 (0.3 to 0.6), and 0.9 (0.5 to 1.5), respectively. Strong, significant risk reduction within 5 years was consistently seen for women and men, younger and older participants, patients with and without high-risk polyps (three or more polyps, at least one polyp ≥ 1 cm, at least one polyp with villous components), and those with and without polypectomy in the right colon. With adjusted odds ratios of 0.1 (0.1 to 0.2), 0.3 (0.2 to 0.5) and 0.4 (0.2 to 0.8) for patients with polypectomy less than 3, 3 to 5, and 6 to 10 years ago, risk reduction was particularly strong for left-sided CRC. CONCLUSION: Extension of surveillance intervals to 5 years should be considered, even after detection and removal of high-risk polyps.

Design and current status of CONTINT: continuous versus interrupted abdominal wall closure after emergency midline laparotomy - a randomized controlled multicenter trial [NCT00544583].

BACKGROUND: The optimal strategy for abdominal wall closure has been an issue of ongoing debate. Available studies do not specifically enroll patients who undergo emergency laparotomy and thus do not consider the distinct biological characteristics of these patients. The present randomized controlled trial evaluates the efficacy and safety of two commonly applied abdominal wall closure strategies in patients undergoing primary emergency midline laparotomy. METHODS/DESIGN: The CONTINT trial is a multicenter, open label, randomized controlled trial with a two-group parallel design. Patients undergoing a primary emergency midline laparotomy are enrolled in the trial. The two most commonly applied strategies of abdominal wall closure after midline laparotomy are compared: the continuous, all-layer suture technique using slowly absorbable monofilament material (two Monoplus loops) and the interrupted suture technique using rapidly absorbable braided material (Vicryl sutures). The primary endpoint within the CONTINT trial is an incisional hernia within 12 months or a burst abdomen within 30 days after surgery. As reliable data on this primary endpoint is not available for patients undergoing emergency surgery, an adaptive interim analysis will be conducted after the inclusion of 80 patients, allowing early termination of the trial if necessary or modification of design characteristics such as recalculation of sample size. DISCUSSION: This is a randomized controlled multicenter trial with a two-group parallel design to assess the efficacy and safety of two commonly applied abdominal wall closure strategies in patients undergoing primary emergency midline laparotomy. TRIAL REGISTRATION: NCT00544583.

Vascular clips versus ligatures in thyroid surgery--results of a multicenter randomized controlled trial (CLIVIT Trial).

BACKGROUND: New techniques using vascular clips or ultrasonically activated shears have been suggested to shorten operation time without compromising safety. The objective of the CLIVIT Trial was to compare ligatures with vascular clips for hemostasis in elective benign thyroid surgery. METHODS: This multicenter, randomized, controlled, parallel group superiority trial was conducted in 13 German surgical centers. Patients scheduled for at least subtotal resection bilaterally were intraoperatively randomized. The primary endpoint was resection time. Secondary endpoints were the amount of postoperative bleeding, reoperation due to bleeding, wound infection, temporary (reversal within 12 months) and permanent (over 1 year) recurrent laryngeal nerve (RLN) paralysis, length of hospital stay, and safety. REGISTRATION: ISRCTN 96901396. RESULTS: Two hundred fifty patients were treated with ligatures and 241 with vascular clips. No differences in patients' baseline and surgical characteristics were observed. No difference was detected for mean resection time (clip 63.5 min ± 29.6, ligature 66.1 min ± 29.3, P = 0.258). Postoperative bleeding (mean 86 ml ± 93), reoperation due to bleeding (clips 4, ligature 2), wound infections (clips 4, ligature 4), postoperative hospital stay (mean 3.0 ± 1.9), and safety data also did not vary significantly. The rates of temporary and permanent RLN paralysis were 6.9 % (34/491) and 2.9 % (14/491), respectively. Not using a surgical drain (123 patients) was not associated with a higher rate of complications. CONCLUSION: Vascular clips did not reduce the resection time. However, a 2.9 % rate of permanent RLN paralysis is of concern. Drains in elective surgery may be of no benefit.

To whom do the results of the multicenter, randomized, controlled INSECT trial (ISRCTN 24023541) apply?--assessment of external validity.

UNLABELLED: A response to Seiler et al: Interrupted or continuous slowly absorbable sutures for closure of primary elective midline abdominal incisions: a multicenter randomized trial (INSECT: ISRCTN24023541). Ann Surg 2009, 249(4):576-582. BACKGROUND: Existing evidence suggests that the transfer of results of randomized controlled trials into clinical practice may be limited. Potential reasons can be attributed to aspects of external validity. The aim of this study is to investigate issues related to the external validity of the INSECT trial. METHODS: All participating surgical departments were categorized and the clinical and baseline characteristics of randomized patients were evaluated. In addition, demographic and clinical data of all screened and randomized patients at the Departments of Surgery in Heidelberg and Erlangen were analyzed. RESULTS: Twenty-five centers enrolled a total of 625 patients. These centers included eight primary, 11 secondary, and six tertiary care centers. The tertiary care centers enrolled the most patients (n = 237, 38%) followed by the primary care centers (n = 199, 32%) and the secondary care centers (n = 189 patients; 30%). The mean number and baseline data of randomized patients did not differ between the three types of care centers (p = 0.09). Overall, the treatment according to protocol was at least 92%. At the Department of Surgery, University of Heidelberg, 307 patients were screened and 60 out of 130 eligible patients were randomized. There were no differences in demographic and clinical baseline data between included and non-included patients. In Erlangen, 351 patients were screened and 57 out of 106 eligible patients randomized. CONCLUSIONS: Results of the INSECT trial are applicable to a broad spectrum of patients treated at different hospital levels.

Clustering in surgical trials--database of intracluster correlations.

BACKGROUND: Randomised trials evaluation of surgical interventions are often designed and analysed as if the outcome of individual patients is independent of the surgeon providing the intervention. There is reason to expect outcomes for patients treated by the same surgeon tend to be more similar than those under the care of another surgeon due to previous experience, individual practice, training, and infrastructure. Such a phenomenon is referred to as the clustering effect and potentially impacts on the design and analysis adopted and thereby the required sample size. The aim of this work was to inform trial design by quantifying clustering effects (at both centre and surgeon level) for various outcomes using a database of surgical trials. METHODS: Intracluster correlation coefficients (ICCs) were calculated for outcomes from a set of 10 multicentre surgical trials for a range of outcomes and different time points for clustering at both the centre and surgeon level. RESULTS: ICCs were calculated for 198 outcomes across the 10 trials at both centre and surgeon cluster levels. The number of cases varied from 138 to 1370 across the trials. The median (range) average cluster size was 32 (9 to 51) and 6 (3 to 30) for centre and surgeon levels respectively. ICC estimates varied substantially between outcome type though uncertainty around individual ICC estimates was substantial, which was reflected in generally wide confidence intervals. CONCLUSIONS: This database of surgical trials provides trialists with valuable information on how to design surgical trials. Our data suggests clustering of outcome is more of an issue than has been previously acknowledged. We anticipate that over time the addition of ICCs from further surgical trial datasets to our database will further inform the design of surgical trials.

Evaluation of the safety and efficacy of MonoMax® suture material for abdominal wall closure after primary midline laparotomy-a controlled prospective multicentre trial: ISSAAC [NCT005725079].

PURPOSE: Different suture techniques and various suture materials are in use to close midline incisions after primary laparotomy. The ISSAAC study aimed to assess the safety and efficacy of the new ultra-long-term absorbable, elastic monofilament suture material MonoMax® for abdominal wall closure. METHODS: This is a single-arm, multicentre prospective study that included 150 patients undergoing a primary elective midline incision. The control group consists of 141 patients from the INSECT study who received MonoPlus® or PDS® for abdominal wall closure. The incidences of burst abdomen and wound infection until the day of discharge were defined as the primary composite endpoints. The rate of incisional hernias 1 year after surgery, the length of postoperative hospital stay and safety parameters served as secondary endpoints. The study has been registered under www.clinicaltrials.gov [NCT005725079]. RESULTS: Eleven patients in the ISSAAC study [7.3%; 95% CI = (3.9; 13.1%)] experienced wound infection or burst abdomen until the day of discharge as compared to 16 [11.3%; 95% CI = (6.6; 17.8%)] patients in the INSECT control group (p = 0.31). The length of postoperative hospital stay was comparable in both study groups. One year after surgery, incisional hernias were observed in 21 ISSAAC patients (14.0%) in contrast to 30 hernias (21.3%) in the INSECT control group. CONCLUSIONS: The ultra-long-term absorbable, elastic monofilament suture material MonoMax® is safe and efficient for abdominal wall closure.

Surgical evaluation and knowledge transfer--methods of clinical research in surgery.

PURPOSE: This article aims to outline the framework of surgical evaluation and knowledge transfer. Therefore, special design issues affecting surgical clinical research will be discussed. Moreover, principles and challenges of knowledge transfer from research into practice will be addressed. BACKGROUND: The ultimate goal of academic surgery is to improve surgical and perioperative care in order to achieve the best outcomes for patients. Randomized controlled trials and reviews with and without meta-analyses are fundamental requirements for evidence-based decision making. DISCUSSION: Despite calls for more rigorous research methods in surgery, the frequency of high-quality randomized controlled trials and systematic reviews is low. Specific methodological and design issues have to be implemented for valid evaluation of surgical procedures. Thus, general catchwords of clinical epidemiology such as timing, randomization, registration, and reporting standards demand special appraisal. Moreover, blinding methods, placebo controls, learning curves, standardized outcome assessment, and generalizability are critical design issues in surgical trials. Moreover, systematic reviews and meta-analyses are desirable for answering clinical issues or defining new research questions. CONCLUSION: For a rigorous evaluation of surgical procedures, a basic understanding of research methodology is urgently needed, and to improve methodological expertise, collaboration between surgeons and methodologists is encouraged.

Interval cancers after negative colonoscopy: population-based case-control study.

OBJECTIVE: The risk of colorectal cancer after a previous negative colonoscopy is very low. Nevertheless, interval cancers occur. We aimed to assess the characteristics and predictors of interval cancers after negative colonoscopy. METHODS: A population-based case-control study was conducted in Southern Germany in 2003-7. Sociodemographic and tumour characteristics were compared among 78 patients with interval cancers occurring 1-10 years after a negative colonoscopy and 433 colorectal cancers detected at screening. In addition, the indication for the preceding negative colonoscopy and its completeness were compared between patients with interval cancers and 515 controls with a preceding negative colonoscopy. RESULTS: 56.4% of interval cancers occurred among women compared with 33.7% of cases detected by screening (p=0.0001). After adjustment for covariates, female sex (OR 2.28, 95% CI 1.35 to 3.83) and location in the caecum or ascending colon (OR 1.98, 95% CI 1.17 to 3.35) were independently associated with occurrence of interval cancers. The preceding negative colonoscopy was more commonly conducted because of a positive faecal occult blood test (26.0% vs 12.9%, p=0.009) and was more often incomplete (caecum not reached: 18.1% vs 6.7%, p=0.001) among interval cancer cases than among controls. Characteristics of the preceding negative colonoscopy strongly and independently associated with occurrence of interval cancers were follow-up of a positive faecal occult blood test among men (OR 5.49, 95% CI 2.10 to 14.35) and incompleteness among women (OR 4.38, 95% CI 1.69 to 11.30). CONCLUSIONS: The observed patterns suggest that a substantial proportion of interval cancers are due to neoplasms missed at colonoscopy and are potentially preventable by enhanced performance of colonoscopy.

Prevention of abdominal wound infection (PROUD trial, DRKS00000390): study protocol for a randomized controlled trial.

BACKGROUND: Wound infection affects a considerable portion of patients after abdominal operations, increasing health care costs and postoperative morbidity and affecting quality of life. Antibacterial coating has been suggested as an effective measure to decrease postoperative wound infections after laparotomies. The INLINE metaanalysis has recently shown the superiority of a slowly absorbable continuous suture for abdominal closure; with PDS plus® such a suture has now been made available with triclosan antibacterial coating. METHODS/DESIGN: The PROUD trial is designed as a randomised, controlled, observer, surgeon and patient blinded multicenter superiority trial with two parallel groups and a primary endpoint of wound infection during 30 days after surgery. The intervention group will receive triclosan coated polydioxanone sutures, whereas the control group will receive the standard polydioxanone sutures; abdominal closure will otherwise be standardized in both groups. Statistical analysis is based on intention-to-treat population via binary logistic regression analysis, the total sample size of n=750 is sufficient to ensure alpha=5% and power=80%, an interim analysis will be carried out after data of 375 patients are available. DISCUSSION: The PROUD trial will yield robust data to determine the effectiveness of antibacterial coating in one of the standard sutures for abdominal closure and potentially lead to amendment of current guidelines. The exploration of clinically objective parameters as well as quality of life holds immediate relevance for clinical management and the pragmatic trial design ensures high external validity. TRIAL REGISTRATION: The trial protocol has been registered with the German Clinical Trials Register (DRKS00000390).