Diagnostic accuracy of urinary intestinal fatty acid binding protein in detecting colorectal anastomotic leakage.

BACKGROUND: Anastomotic leakage (AL) remains a severe complication following colorectal surgery, having a negative impact on both short- and long-term outcomes. Since timely detection could enable early intervention, there is a need for the development of novel and accurate, preferably, non-invasive markers. The aim of this study was to investigate whether urinary intestinal fatty acid binding protein (I-FABP) could serve as such a marker. METHODS: This prospective multicenter cross-sectional phase two diagnostic study was conducted at four centers in the Netherlands between March 2015 and November 2016. Urine samples of 15 patients with confirmed colorectal AL and 19 patients without colorectal AL on postoperative day 3 were included. Urinary I-FABP levels were determined using enzyme-linked immunosorbent assays and adjusted for urinary creatinine to compensate for renal dysfunction. RESULTS: Urinary I-FABP levels were significantly elevated in patients with confirmed AL compared to patients without AL on postoperative day 3 (median: 2.570 ng/ml vs 0.809 ng/ml, p = 0.006). The area under the receiver operating characteristics curve (AUROC) was 0.775, yielding a sensitivity of 80% and specificity of 74% at the optimal cutoff point (> 1.589 ng/ml). This difference remained significant after calculation of I-FABP/creatinine ratios (median: 0.564 ng/µmol vs. 0.158 ng/µmol, p = 0.040), with an AUROC of 0.709, sensitivity of 60% and specificity of 90% at the optimal cutoff point (> 0.469 ng/µmol). CONCLUSIONS: Levels of urinary I-FABP and urinary I-FABP/creatinine were significantly elevated in patients with confirmed AL following colorectal surgery, suggesting their potential as a non-invasive biomarker for colorectal anastomotic leakage.

Urinary volatile organic compound markers and colorectal anastomotic leakage.

AIM: Inflammatory markers such as serum C-reactive protein (CRP) are used as routine markers to detect anastomotic leakage following colorectal surgery. However, CRP is characterized by a relatively low predictive value, emphasizing the need for the development of novel diagnostic approaches. Volatile organic compounds (VOCs) are gaseous metabolic products deriving from all conceivable bodily excrements and reflect (alterations in) the patient's physical status. Therefore, VOCs are increasingly considered as potential non-invasive diagnostic biomarkers. The aim of this study was to assess the diagnostic accuracy of urinary VOCs for colorectal anastomotic leakage. METHODS: In this explorative multicentre study, urinary VOC profiles of 22 patients with confirmed anastomotic leakage and 27 uneventful control patients following colorectal surgery were analysed by field asymmetric ion mobility spectrometry (FAIMS). RESULTS: Urinary VOCs of patients with anastomotic leakage could be distinguished from those of control patients with high accuracy: area under the receiver operating characteristics curve 0.91 (95% CI 0.81-1.00, P < 0.001), sensitivity 86% and specificity 93%. Serum CRP was significantly increased in patients with a confirmed anastomotic leak but with lower diagnostic accuracy compared to VOC analysis (area under the receiver operating characteristics curve 0.82, 95% CI 0.68-0.95, P < 0.001). Combining VOCs and CRP did not result in a significant improvement of the diagnostic performance compared to VOCs alone. CONCLUSION: Analysis by FAIMS allowed for discrimination between urinary VOC profiles of patients with a confirmed anastomotic leak and control patients following colorectal surgery. A superior accuracy compared to CRP and apparently high specificity was observed, underlining the potential as a non-invasive biomarker for the detection of colorectal anastomotic leakage.

Small bowel obstruction, incisional hernia and survival after laparoscopic and open colonic resection (LAFA study).

BACKGROUND: Short-term advantages to laparoscopic surgery are well described. This study compared medium- to long-term outcomes of a randomized clinical trial comparing laparoscopic and open colonic resection for cancer. METHODS: The case notes of patients included in the LAFA study (perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care) were reviewed 2-5 years after randomization for incisional hernia, adhesional small bowel obstruction (SBO), overall survival, cancer recurrence and quality of life (QoL). The laparoscopic and open groups were compared irrespective of fast-track or standard perioperative care. RESULTS: Data on incisional hernias, SBO, survival and recurrence were available for 399 of 400 patients: 208 laparoscopic and 191 open resections. These outcomes were corrected for duration of follow-up. Median follow-up was 3·4 (i.q.r. 2·6-4·4) years. Multivariable regression analysis showed that open resection was a risk factor for incisional hernia (odds ratio (OR) 2·44, 95 per cent confidence interval (c.i.) 1·12 to 5·26; P = 0·022) and SBO (OR 3·70, 1·07 to 12·50; P = 0·039). There were no differences in overall survival (hazard ratio 1·10, 95 per cent c.i. 0·67 to 1·80; P = 0·730) or in cumulative incidence of recurrence (P = 0·514) between the laparoscopic and open groups. There were no measured differences in QoL in 281 respondents (P > 0·350 for all scales). CONCLUSION: Laparoscopic colonic surgery led to fewer incisional hernia and adhesional SBO events. REGISTRATION NUMBER: NTR222 (http://www.trialregister.nl).

Multidisciplinary discussion and management of rectal cancer: a population-based study.

BACKGROUND: The purpose of the present study was to evaluate the value of discussing rectal cancer patients in a multidisciplinary team (MDT). METHODS: All treated rectal cancer patients (>T1M0) diagnosed in 2006-2008 were included. According to the national guidelines, neoadjuvant (chemo)radiotherapy should be given to all rectal cancer patients. Patients were scored as "discussed" (MDT+) only if documented proof was available. The primary endpoint was the number of positive circumferential resection margins (CRM ≤ 1 mm). RESULTS: Of the 275 patients included, 210 were analyzed (exclusions: (recto)sigmoid tumor, acute laparotomy, and inoperability). Neoadjuvant treatment was applied in 174 (83%) patients and followed by total mesorectal excision in 171 (81%) patients. Patients considered not to require downstaging, received short-course radiotherapy (SCRT) (n = 116) or no radiotherapy (no RT) (n = 36), whereas 58 more advanced patients received chemoradiotherapy (CRT). The MDT discussion took place in 116 cases (55%). In the MDT+ group an MRI was used more often (p = 0.001) and TNM staging was more complete (p < 0.001). The proportion of patients with advanced disease was higher in the MDT+ group (88% ≥T3/N+ versus 68%; p = 0.001). The overall CRM+ rate was 13% and did not differ between the MDT+ and the MDT- group (p = 0.392). In patients receiving SCRT or no RT, the CRM+ rate was 10%, whereas the rate was 20% for patients receiving CRT. CONCLUSIONS: Although no difference in CRM+ rate was found for those patients who were discussed and those who were not, our results demonstrate room for improvement, especially in the selection of patients for SCRT or no RT. We advocate standardized documentation of treatment decisions and pathology reports.

A rare complication after laparoscopic gastric banding: connecting-tube penetration into the hilus of the kidney.

Laparoscopic adjustable gastric banding is a common operation for morbid obesity. Late complications mainly originate from either the injection port (dislocation, infection, leakage) or the gastric band (pouch dilatation, slippage, leakage, gastric erosion). Complications from the tube, connecting the port with the band, are rarely described. We report the penetration of a loose connecting tube into the kidney 8 months after removal of an infected injection port.

Systematic review of laparoscopic vs open colonic surgery within an enhanced recovery programme.

BACKGROUND: Fast track surgery accelerates recovery, reduces morbidity and shortens hospital stay. It is unclear what the effects are of laparoscopic or open surgery within a fast track programme. The aim of this systematic review was to review the existing evidence. METHOD: A systematic review was performed of all randomized (RCTs) and controlled clinical trials (CCTs) on laparoscopic and open surgery within a fast track setting. Primary endpoints were primary and overall hospital stay, readmission rate, morbidity and mortality. Study selection, quality assessment and data extraction were performed independently by two observers. RESULTS: Only two RCTs and three CCTs were eligible for final analysis, which reported on 400 patients. Data could not be pooled because of clinical heterogeneity. One RCT and one CCT stated a shorter primary hospital stay in the laparoscopic group of 3 and 2 days, respectively. In one RCT, the readmission rate was lower in the laparoscopic group; absolute risk reduction (ARR) 21.4% [95% confidence interval (CI): 6-42.3%] resulting in a number needed to treat (NNT) of 4.7 patients (95% CI: 2.4-176). Another study showed a 23% difference in favour of the laparoscopic group with regard to morbidity (95% CI: 6.3-39.1%), i.e. an NNT of 4.4 patients (95% CI: 2.6-15.9). There were no significant differences in mortality rates. CONCLUSION: Due to the present lack of data, no robust conclusions can be made. A large randomized controlled trial is required to compare laparoscopic with open surgery within a fast track setting.

Pharyngolaryngoesophagectomy using the thoracoscopic approach.

BACKGROUND: Thoracoscopic mobilization of the esophagus for pharyngolaryngoesophagectomy allows dissection under direct vision, and therefore it potentially results in fewer complications than conventional transhiatal mobilization. In this article we report our experience with this approach. It was also hypothesized that a learning curve existed and that results have improved over time. PATIENTS AND METHODS: From July 1994 until January 2004, 57 patients underwent pharyngolaryngoesophagectomy in our institution. Intraoperative events and postoperative outcome were prospectively documented, and long-term follow-up data were also studied. Results were compared between the first 30 patients and the last 27 patients. RESULTS: There were no significant differences between the two groups with respect to the various clinicopathological characteristics. There was no difference in the median thoracoscopic time between the first 30 and last 27 patients at 90 and 75 min, respectively, p = 0.18. For the complete procedure there was significantly less blood loss in the later group; median (range) blood loss 700 (164-3000) ml versus 400 (100-1200) ml, p = 0.002. Overall pulmonary complications occurred in 12 patients (40%) in the first group versus 13 (48%) in the second group, p = 0.6. The incidence of atrial arrhythmia was also similar, affecting 6 (20%) patients and 3 (11%), respectively, p = 0.47. Hospital mortality rates were 13.3% and 7.4%, p = 0.67. Two-year survival rates were no different (46% versus 45% p = 0.85). CONCLUSIONS: Although, subjectively, operating skills have improved over time, better results in the second half of this series could not be demonstrated clearly, likely because the operating surgeons had prior extensive experience in esophageal and thoracoscopic procedures.

New insights in the lymphatic spread of oesophageal cancer and its implications for the extent of surgical resection.

In this review new insights in the dissemination pattern of oesophageal tumours and the implications for the (extent of) surgical and endoscopic resection are discussed. Moreover, the sentinel node concept in oesophageal cancer is reconsidered. Three-years survival after a limited resection for cervical-upper thoracic oesophageal cancer was 14-20% after an extended resection. No patients with distant metastases were alive after five years. Therefore, curative surgery for cervical-upper oesophageal cancer with extended lymph node dissection is probably only indicated in patients without distant lymph nodes metastases. Involved coeliac nodes can be found in tumours of the whole oesophagus. Adenocarcinomas of the gastrooesophageal junction do metastasize predominantly to the paracardial and lesser curvature regions. No significant difference was found in a randomized trial comparing two-field transthoracic resection with limited transhiatal resection for adenocarcinoma of the gastrooesophageal junction.(6) Subgroup analysis for patients with a distal oesophageal adenocarcinoma revealed a 17% survival benefit after transthoracic resection. In several Japanese studies a better five-year survival is claimed after a three-field lymph node dissection than after a conventional two-field lymphadenectomy. In a randomized study, however, no statistically significant difference was found in the short- and long-term survival nor in the recurrence rate. If an early lesion is limited to the mucosa, endoscopic mucosal resection (EMR) could be considered because of the low chance of lymph node metastases. However, the technique of EMR has not yet been optimized resulting in high numbers of local cancer recurrences and a high need for endoscopic re-resections. Only few studies investigated whether the sentinel node concept is applicable to the oesophagus or gastric cardia. In one study in patients with oesophageal or cardia cancer, the accuracy was 96% and only two false negative sentinel nodes were identified. The sentinel node concept in oesophageal cancers might change future operative strategies.

[Mesenteric venous thrombosis during pregnancy; a rare cause of acute ischaemia of the small intestine]. / Veneuze mesenteriale trombose tijdens de zwangerschap.

BACKGROUND: Acute ischaemia of the small intestine is caused by mesenteric venous thrombosis in 5-15% of patients. The non-specific symptoms frequently lead to a diagnostic delay. CASE DESCRIPTION: A 30-year-old pregnant woman presented at the accident and emergency department with progressive abdominal pain, nausea and vomiting. During admission the patient developed signs of peritonitis. Diagnostic laparoscopy revealed a picture of mesenteric venous thrombosis, and we resected 170 cm ischemic small intestine. No underlying cause was identified, apart from the pregnancy. The patient was treated with low-molecular-weight heparin and later gave birth to a healthy child. CONCLUSION: If a patient presents with (unexplained) progressive abdominal symptoms and disproportional abdominal pain without peritonitis, the possibility of intestinal ischaemia should be considered during differential diagnosis.

Molecular evidence of field cancerization in a patient with 7 tumors of the aerodigestive tract.

Exposure of the mucosa of the upper aerodigestive tract to carcinogens can induce genetic changes resulting in various independent clones of neoplastic growth, a concept defined as "field cancerization." The risk of developing multiple tumors in this compartment of the body is well established. We studied 6 distinct tumors of the upper aerodigestive tract of a single patient for loss of heterozygosity (LOH), microsatellite instability (MSI), p53 mutations, and K-ras codon 12 point mutations. We detected a unique pattern of LOH and p53 mutations in all 6 tumors. No tumor showed a K-ras mutation or MSI. The results support the mechanism of "field cancerization" and illustrate the potential power of molecular techniques to elucidate pathogenesis.

Nipple-sparing mastectomy in breast cancer: a viable option?

BACKGROUND: In women with breast cancer for whom breast-conserving therapy (BCT) is not the best option, a nipple and areola complex-(NAC) sparing mastectomy with immediate reconstruction has been proposed as a good and safe alternative to conventional, more radical mastectomy. Surgeons hesitate to perform this operation for fear of recurrence of tumour in the NAC due to undetected nipple involvement (NI) of the tumour. In order to determine whether a NAC-sparing mastectomy is a viable option, the frequency and predictive factors of NI by the tumour were studied in the literature. METHODS: A literature survey was performed by searching the Medline database. Other references were derived from the material perused. RESULTS AND CONCLUSIONS: NI is found in up to 58% of mastectomy specimens and correlates with tumour size, tumour-areola or tumour-nipple distance, positive lymph nodes and clinical suspicion. Best candidates for NAC-sparing mastectomy are patients with a small tumour (T1) at a large distance (>4-5 cm) from the nipple. However, in these patients BCT has excellent results with low complications and recurrence rates. Considering the incidence of NI in larger tumours (T2 average 33%, T3 average >50%) a NAC-sparing mastectomy may carry an unacceptable high risk for local relapse and should therefore not be advocated.

The impact of surgical complications as a main risk factor for venous thromboembolism: a multicenter study.

BACKGROUND: Studies suggest that postoperative complications are a risk factor for venous thromboembolism (VTE) after bariatric surgery. Knowledge of factors associated with a higher risk of VTE after bariatric surgery may be essential to select patients who may benefit from either prolonged or intensified thrombosis prophylaxis. The aim of this study is to determine the relationship between postoperative complications and VTE after bariatric surgery and other classical risk factors. METHODS: A retrospective multicenter case-control study was performed in patients who had bariatric surgery between January 2008 and September 2011. VTE until 6 months after surgery was registered, and patients were contacted to ascertain the results. For every case of VTE after surgery, 6 control patients were selected who were matched for gender, age, participating center and type of surgery. Risk factors for VTE before and after surgery and postoperative complications were registered. RESULTS: A total of 2,064 surgeries were included. In 12 patients, VTE occurred within 6 months after bariatric surgery (incidence 0.58 %, 95 % confidence interval (CI) = 0.25-0.93). There was a strong association of complications after surgery (cases 91.7 %, controls 15.3 %, odds ratio (OR) 61.0; 95 % CI = 7.1-521.3) or intensive care admission (cases 50.0 %, controls 11.1 %, OR = 8.0; 95 % CI = 2.1-30.8) with VTE. The majority of postoperative complications were anastomotic leak, abdominal abscess, and infection. We could not detect an association between classical thrombosis risk factors and postoperative VTE. CONCLUSIONS: The incidence of VTE is low after bariatric surgery using thrombosis prophylaxis. However, there is a strong association between postoperative complications and VTE. These patients may benefit from more intensive thrombosis prophylaxis.

Bariatric surgery is an effective treatment for morbid obesity.

The global obesity epidemic is also affecting the Netherlands, paralleled by a proportional increase in the number of morbidly obese persons. Bariatric surgery has been included as a treatment for morbid obesity in the Dutch Guideline for Obesity (2008). Nonetheless, bariatric surgery is applied in only a limited number of morbidly obese subjects in the Netherlands. Based on the most recent literature and Dutch statistics, this review provides a summary of current knowledge on the impact of obesity on health and health care and highlights the effective role of bariatric surgery in reducing this threat to public health.

Results of the combination of open transthoracic esophagectomy with laparoscopic gastric tube formation for esophageal cancer.

BACKGROUND: Postoperative complications after open transthoracic esophagectomy could possibly be reduced if the abdominal phase is performed laparoscopically. The aim of this study was to investigate the feasibility of laparoscopic mobilization of the stomach and gastric tube formation in patients undergoing an open transthoracic esophagectomy for cancer. METHODS: Thirteen patients underwent an open transthoracic esophagectomy with extended en bloc lymphadenectomy combined with laparoscopic gastric tube formation. Clinicopathological data were derived from a prospective database and patient files. RESULTS: The median operation time was 484 min (range 347-573) and the median intraoperative blood loss was 1,500 ml (range 250-3,700). In 2 patients the laparoscopic procedure was converted to a laparotomy because of technical difficulties. Median postoperative stay in the ICU was 3 days (range 1-8) and median hospital stay was 29 days (range 12-104). One patient died in the hospital. Postoperatively 3 patients suffered from anastomotic leakage, 5 from pneumonia and 3 from vocal cord palsy. CONCLUSIONS: The complication rate was high in this series of patients undergoing an open extended transthoracic esophagectomy with laparoscopic mobilization of the stomach and gastric tube formation. Laparoscopic mobilization of the stomach and gastric tube formation are feasible, but need carefully guided testing before this technique can be applied routinely.

Effects of prolonged intensive care unit stay on quality of life and long-term survival after transthoracic esophageal resection.

OBJECTIVE: There are few prospective data on the effects of prolonged intensive care unit stay on the quality of life and long-term survival of a homogeneous patient population. Therefore, the aims of this prospective study were a) to describe the quality of life in patients after having a transthoracic esophageal resection; and b) to analyze the influences of a prolonged intensive care unit stay on quality of life and survival in patients after esophageal cancer resection who survived to hospital discharge. DESIGN: Prospective study. SETTING: Medical center. PATIENTS: The study population consisted of 109 patients undergoing a transthoracic resection for adenocarcinoma of the middistal esophagus or gastric cardia between April 1994 and February 2000. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A comparison was made between patients staying or=6 days in the intensive care unit and also or=14 days. Quality of life was assessed in all patients by mailed self-report questionnaires at baseline (preoperatively), at 5 wks, and at 3, 6, 9, 12, 18, 24, 30, and 36 months after surgery. Daily physical, emotional, and social functioning was assessed with the generic Medical Outcome Studies Short Form-20. Disease-specific quality of life was measured by an adapted Rotterdam Symptom Check List. Quality of life data were gathered between July 1994 and March 2003. Five of the 109 patients died in the hospital and were excluded from the analysis. All five of them were in the intensive care unit >or=6 days. Of the remaining 104 patients, 92 provided baseline scores. The data of the 92 patients were used for the quality of life analyses. For the clinicopathologic and survival analysis, the data of 104 hospital survivors were used. Patients spent a median of 5.5 days (range 0-71) in the intensive care unit. The Medical Outcome Studies Short Form-20 and the Rotterdam Symptom Check List measurements showed no clear differences in long-term quality of life between patients after a short vs. a prolonged postoperative intensive care unit period. The median overall survival in all patients was 2.0 yrs (range 0.1-8.0). Median overall survival in patients staying in the intensive care unit or=6 days (p = .9, log-rank test). Median overall survival in patients staying in the intensive care unit or=14 days (p = .74, log-rank test). CONCLUSIONS: For patients who survived to hospital discharge after transthoracic esophagectomy, there was no difference in long-term quality of life or survival between those submitted to the intensive care unit for a short period vs. a long period.

Prospective analysis of patients with adenocarcinoma of the gastric cardia and lymph node metastasis in the proximal field of the chest.

BACKGROUND: The extent to which adenocarcinoma of the cardia with lymph node metastasis in the upper mediastinum is amenable to cure by radical surgery is open to debate. It remains unclear whether these relatively distant metastases have an effect on long-term survival. The aim of this study was to identify the incidence of such positive nodes and evaluate their prognostic significance. METHODS: Some 50 patients with adenocarcinoma of the gastric cardia and substantial invasion of the oesophagus (junctional type II), who underwent an extended transthoracic oesophagectomy as part of a prospective randomized trial between 1994 and 2000, were studied. RESULTS: Eleven patients (22 per cent) had lymph node metastasis in the proximal field of the chest. These patients had more positive nodes overall (P = 0.020) and a shorter median survival (P = 0.009) than those without such metastasis. Multivariate analysis identified positive nodes in the proximal field as an independent predictor of poor survival. CONCLUSION: Lymph node metastasis in the proximal field of the chest is common and is an indicator of poor prognosis in patients with adenocarcinoma of the cardia.