A preoperative prediction model for anastomotic leakage after rectal cancer resection based on 13.175 patients.

INTRODUCTION: This study aims to develop a robust preoperative prediction model for anastomotic leakage (AL) after surgical resection for rectal cancer, based on established risk factors and with the power of a large prospective nation-wide population-based study cohort. MATERIALS AND METHODS: A development cohort was formed by using the DCRA (Dutch ColoRectal Audit), a mandatory population-based repository of all patients who undergo colorectal cancer resection in the Netherlands. Patients aged 18 years or older were included who underwent surgical resection for rectal cancer with primary anastomosis (with or without deviating ileostomy) between 2011 and 2019. Anastomotic leakage was defined as clinically relevant leakage requiring reintervention. Multivariable logistic regression was used to build a prediction model and cross-validation was used to validate the model. RESULTS: A total of 13.175 patients were included for analysis. AL was diagnosed in 1319 patients (10%). A deviating stoma was constructed in 6853 patients (52%). The following variables were identified as significant risk factors and included in the prediction model: gender, age, BMI, ASA classification, neo-adjuvant (chemo)radiotherapy, cT stage, distance of the tumor from anal verge, and deviating ileostomy. The model had a concordance-index of 0.664, which remained 0.658 after cross-validation. In addition, a nomogram was developed. CONCLUSION: The present study generated a discriminative prediction model based on preoperatively available variables. The proposed score can be used for patient counselling and risk-stratification before undergoing rectal resection for cancer.

A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection.

AIM: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. METHOD: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1ß), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. RESULTS: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0-14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78). CONCLUSION: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool.

Transanal total mesorectal excision: how are we doing so far?

AIM: This subgroup analysis of a prospective multicentre cohort study aims to compare postoperative morbidity between transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LaTME). METHOD: The study was designed as a subgroup analysis of a prospective multicentre cohort study. Patients undergoing TaTME or LaTME for rectal cancer were selected. All patients were followed up until the first visit to the outpatient clinic after hospital discharge. Postoperative complications were classified according to the Clavien-Dindo classification and the comprehensive complication index (CCI). Propensity score matching was performed. RESULTS: In total, 220 patients were selected from the overall prospective multicentre cohort study. After propensity score matching, 48 patients from each group were compared. The median tumour height for TaTME was 10.0 cm (6.0-10.8) and for LaTME was 9.5 cm (7.0-12.0) (P = 0.459). The duration of surgery and anaesthesia were both significantly longer for TaTME (221 vs 180 min, P < 0.001, and 264 vs 217 min, P < 0.001). TaTME was not converted to laparotomy whilst surgery in five patients undergoing LaTME was converted to laparotomy (0.0% vs 10.4%, P = 0.056). No statistically significant differences were observed for Clavien-Dindo classification, CCI, readmissions, reoperations and mortality. CONCLUSION: The study showed that TaTME is a safe and feasible approach for rectal cancer resection. This new technique obtained similar postoperative morbidity to LaTME.

Multicentre study of non-surgical management of diverticulitis with abscess formation.

This multicentre retrospective cohort study included 447 patients with Hinchey Ib and II diverticular abscesses, who were treated with antibiotics, with or without percutaneous drainage. Abscesses of 3 and 5 cm in size were at higher risk of short-term treatment failure and emergency surgery respectively. Initial non-surgical treatment of Hinchey Ib and II diverticular abscesses was comparable between patients treated with antibiotics only and those who underwent percutaneous drainage in combination with antibiotics, with regard to short- and long-term outcomes. Most do not need drainage.

Incidence, risk factors and prevention of stoma site incisional hernias: a systematic review and meta-analysis.

AIM: Stoma reversal might lead to a stoma site incisional hernia. Recently, prophylactic mesh reinforcement of the stoma site has gained increased attention, supporting the need for accurate data on the incidence of and risk factors for stoma site incisional hernia and to identify high-risk patients. The aim of this study was to assess incidence, risk factors and prevention of stoma site incisional hernias. METHOD: Embase, MEDLINE, Web of Science, Cochrane and Google Scholar databases were searched. Studies reporting the incidence of stoma site incisional hernia after stoma reversal were included. Study quality was assessed with the Newcastle-Ottawa Scale and Cochrane risk of bias tool. Data on incidence, risk factors and prophylactic mesh reinforcement were extracted. RESULTS: Of 1440 articles found, 33 studies comprising 4679 reversals were included. The overall incidence of incisional hernia was 6.5% [range 0%-38%, median follow-up 27.5 (17.54-36) months]. Eleven studies assessed stoma site incisional hernia as the primary end-point, showing an incidence of 17.7% [range 1.7%-36.1%, median follow-up 28 (15.25-51.70) months]. Body mass index, diabetes and surgery for malignant disease were found to be independent risk factors, as derived from eight studies. Two retrospective comparative cohort studies showed significantly lower rates of stoma site incisional hernia with prophylactic mesh reinforcement compared with nonmesh controls [6.4% vs 36.1% (P = 0.001); 3% vs 19% (P = 0.04)]. CONCLUSION: Stoma site incisional hernia should not be underestimated as a long-term problem. Body mass index, diabetes and malignancy seem to be potential risk factors. Currently, limited data are available on the outcomes of prophylactic mesh reinforcement to prevent stoma site incisional hernia.

Systemic Inflammatory Cytokines Predict the Infectious Complications but Not Prolonged Postoperative Ileus after Colorectal Surgery.

AIM: Postoperative ileus (POI) is common after surgery. Animal studies indicate that the POI mechanism involves an inflammatory response, which is also activated during postoperative complications. This study aimed to determine whether inflammatory biomarkers might facilitate an early detection of prolonged POI (PPOI) or infectious complications. METHODS: Forty-seven adult patients who underwent oncological colorectal surgery were included. They filled out a perioperative diary to report their gastrointestinal symptoms. Blood samples were collected preoperatively, and on postoperative day (POD) 1 and 3. Levels of leucocytes, C-reactive protein (CRP), interleukin (IL)-6, TNF-α, and IL-1ß were analyzed. RESULTS: Patients with PPOI had significantly longer stay in hospital than patients without (13.6 ± 10.5 versus 7.4 ± 3.2 days, p < 0.001); they also had higher levels of IL-6 ratios, leucocytes, and CRP levels, but did not reach significance. Higher levels of postoperative IL-6 and CRP levels (p < 0.05, resp.) were found in patients with infectious complications. The receiver operating characteristic (ROC) analysis found better diagnostic values of IL-6 ratio on both POD 1 and 3 than that of CRP (POD 1: ROC 0.825, p < 0.001). CONCLUSION: Blood levels of inflammatory cytokines cannot predict PPOI after colorectal surgery. Instead, postoperative IL-6 changes may predict the infectious complications with a better diagnostic value than the current leukocytes or CRP tests.

Non-operative treatment as a strategy for patients with parastomal hernia: a multicentre, retrospective cohort study.

AIM: Parastomal hernia is the most common complication following stoma construction. Surgical treatment is usually chosen over non-operative treatment, but a clear rationale for the choice of management is often lacking. This study aims to investigate the reasons for non-operative treatment, cross-over rates and postoperative complications. METHOD: A multicentre, retrospective cohort study was conducted. Patients diagnosed with a parastomal hernia between January 2007 and December 2012 were included. Data on baseline characteristics, primary surgery and hernias were collected. For non-operative treatment, reasons for this treatment and cross-over rates were evaluated. For all patients undergoing surgery (surgical treatment and cross-overs), complication and recurrence rates were analysed. RESULTS: Of the 80 patients included, 42 (53%) were in the surgical treatment group and 38 (48%) in the non-operative treatment group. Median follow-up was 46 months (interquartile range 24-72). The reasons for non-operative treatment were absence of symptoms in 12 patients (32%), comorbidities in nine (24%) and patient preference in three (7.9%). In 14 patients (37%) reasons were not documented. Eight patients (21%) crossed over from non-operative treatment to surgical treatment, of whom one needed emergency surgery. In 23 patients (55%), parastomal hernia recurred after the original surgical treatment, of whom 21 (91%) underwent additional repair. CONCLUSION: Parastomal hernia repair is associated with high recurrence and additional repair rates. Non-operative treatment has a relatively low cross-over and emergency surgery rate. Given these data, non-operative treatment might be a better choice for patients without complaints or with comorbidities.

[An image says more than a thousand words; standardising video registration in the operating theatre]. / Een beeld zegt meer dan 1000 woorden.

Today, video imaging is a major part of laparoscopic surgery. Despite continuous efforts to improve or innovate laparoscopic techniques, the registration of laparoscopic imaging for quality of care purposes remains an afterthought. By recording the essential steps of a surgical procedure, it is possible to inquire in more detail about what actually occurred in the operating theatre. However, it is necessary to take the legal framework into account. Questions concerning patient consent, permission from healthcare providers, whether video documentation should enter the patient record, and the length of the period it is retained must be answered. Also, the prevention of the misuse of information is important and therefore the purpose of documentation needs to be put on record beforehand. Video documentation is a promising method of registering surgical quality. However, the first priority is to demonstrate the actual quality improvement of video documentation and the formulation of precise guidelines.

Imaging for Quality Control: Comparison of Systematic Video Recording to the Operative Note in Colorectal Cancer Surgery. A Pilot Study.

BACKGROUND: Oncological and functional results after colorectal cancer surgery vary considerably between hospitals and surgeons. At present, the only source of technical information about the surgical procedure is the operative note, which is subjective and omits critical information. This study aimed to evaluate the feasibility of operative video recording in demonstrating both objective information concerning the surgical procedure and surgical quality, as using a systematic approach might improve surgical performance. METHODS: From July 2015 through November 2015, patients aged ≥18 years undergoing elective colorectal cancer surgery were prospectively included in a single-institution trial. Video recording of key moments was performed peroperatively and analyzed for adequacy. The study cases were compared with a historic cohort. Video was compared with the operative note using the amount of adequate steps and a scoring system. RESULTS: This study compared 15 cases to 32 cases from the historic control group. Compared to the written operative note alone, significant differences in availability of information were seen in favor of video as well as using a combination of video plus the operative note (N adequate steps p = .024; p = <.001. Adequacy score: p = .039; p = <.001, both respectively). CONCLUSIONS: Systematic video registration is feasible and seems to improve the availability of essential information after colorectal cancer surgery. In this respect, combining video with a traditional operative note would be the best option. A multicenter international study is being organized to further evaluate the effect of operative video capture on surgical outcomes.

Improved diagnosis and treatment of anastomotic leakage after colorectal surgery.

AIM: This study aimed at testing feasibility of a standardised postoperative surveillance protocol to reduce delay in the diagnosis of anastomotic leakage (AL) and, subsequently, mortality. MATERIAL AND METHODS: Patient files of patients operated between 1996 and 1999 were reviewed and used as historical controls (n=1066). As a result, a protocol for standardised post-operative surveillance was designed using easily accessible, clinical parameters. Between August 2004 and August 2006, all operated patients with a colorectal anastomosis (n=223) were prospectively subjected to this standardised surveillance. RESULTS: AL was diagnosed in 7.0% of patients in the historical control group and 9.4% of patients in the standardised surveillance group. AL mortality decreased from 39% to 24% with standardised surveillance (n.s.). The delay in AL diagnosis was significantly reduced during standardised surveillance (4 versus 1.5 days, p=0.01), which was confirmed in the multivariate analysis. CONCLUSION: With non-standardised postoperative monitoring, AL was associated with a high mortality rate. Patients were subjected to several additional tests, which were not primarily useful to diagnose AL. Standardised postoperative surveillance for AL was introduced successfully and resulted in a shorter delay between the first signs and symptoms to the confirmation of AL.

[Diagnostic image (369). A Crohn patient with vomiting and diarrhoea]. / Diagnose in beeld (369). Een crohn-patiënt met braken en diarree.

A 79-year-old woman who had been treated surgically for Crohn's disease long ago, presented with vomiting and diarrhoea due to intestinal obstruction by 2 enteroliths.

[Diagnostic image (277). A woman with epigastric pain 10 years after a mastectomy]. / Diagnose in beeld (277). Een vrouw met pijn in epigastrio 10 jaar na een mastectomie.

A 59-year-old woman presented with epigastric pain due to peritonitis carcinomatosa caused by breast cancer diagnosed and surgically treated 10 years earlier.

Variability in TRBV haplotype frequency and composition in Caucasian, African American, Western African and Chinese populations.

The polymorphic T-cell receptor Vbeta (TRBV) genes encode much of the variable region of the T-cell receptor beta chain. Analysis of allele frequencies of three closely linked polymorphic TRBV genes, TRBV7-3, TRBV9 and TRBV6-4, was undertaken in several populations. The frequencies of these alleles are not significantly different in populations of Caucasians, African Americans and Western Africans. However, Chinese population is extremely homogenous at all three loci. The current study identifies the existence of haplotypic relationships between alleles of these genes in the Caucasian population. The ORF allele TRBV7-3*A3 is found exclusively on chromosomes bearing TRBV9*A2 and TRBV6-4*A2 in this cohort. In contrast, TRBV7-3*A1 and the null allele TRBV7-3*A2 are associated only with TRBV9*A1 and TRBV6-4*A1. This pattern of linkage disequilibrium (LD) is altered in the African American and Western African populations. In these cohorts, there is a marked reduction in LD between alleles of TRBV7-3 and TRBV9. This study is consistent with previous population genetic studies wherein African-derived samples have a greater level of genetic diversity compared to Caucasians. These data also demonstrate that patterns of LD are not consistent across the entire TRBV locus.

[Diagnostic image (245). A 2-year-old boy with an acute abdomen]. / Diagnose in beeld (245). Een 2-jarige jongen met een acute buik.

A 2-year-old boy presented at the emergency room with a surgical abdomen and respiratory and circulatory insufficiency caused by a volvulus of the short bowel around a string from a Meckel's diverticulum.

Natural killer cells infiltrating colorectal cancer and MHC class I expression.

A majority of colorectal adenocarcinomas displays diminished MHC class I expression, making them particularly vulnerable for NK cell-mediated killing. Generally, these tumors also show a substantial inflammatory infiltrate. Most inflammatory cells, however, reside in the tumor stroma, where they do not have direct contact with tumor cells in the tumor epithelium. In this study, we investigated the correlation between colorectal tumor MHC class I aberrations and infiltration of NK cells. We studied 88 tumor specimens obtained from 88 colorectal cancer patients for locus-specific HLA aberrations and correlated these data to infiltration of CD4, CD8+ and CD56+ lymphocytes. The lymphocyte markers were individually combined with laminin as a second marker to facilitate quantification in the different tumor compartments, i.e. tumor epithelium and tumor stroma. Locus-specific partial or total HLA class I loss was detected in 72% of the tumors studied. Twenty-eight percent had no HLA loss at all. Mean overall intra-epithelial infiltration of CD56+ lymphocytes was 7 cells/mm(2) compared to 76 cells/mm(2) for CD8 and 19 cells/mm(2) for CD4+ lymphocytes. Locus-specific partial or total loss of tumor cell MHC class I expression was positively correlated with the intra-epithelial infiltration of CD8+ cells (P = 0.01), but not with CD4+ or CD56+ lymphocytes. Triple immunofluorescence staining showed that these cells were CD8 and granzyme-B positive T-lymphocytes. Our data showed that colorectal tumors are sparsely infiltrated by CD56+ cells compared to CD8+ T-cells and that loss of MHC is associated with T-cell infiltration instead of NK cell infiltration. Considering the fact that MHC loss is quite common in colorectal cancer and that, due to local absence of NK cells, it is unlikely that there has been selection for NK-escape variants, improvement of the intra-epithelial infiltration/migration of NK cells may be an important basis for the development of an effective adjuvant NK-based immunotherapy of colorectal cancer.

Dendritic cells in colorectal cancer correlate with other tumor-infiltrating immune cells.

Dendritic cells (DCs) are the most efficient antigen-presenting cells and play a key role in a cellular antitumor immune response. In this study we investigated the exact localization of DCs within colorectal tumors and their relationship to tumor-infiltrating lymphocytes as well as clinical outcome of the patients. Primary tumor specimens of 104 patients with a diagnosis of colorectal cancer were identified retrospectively and analyzed with the dendritic cell markers S-100 protein and human leukocyte antigens (HLA) class II. The markers were individually combined with laminin as a second marker to facilitate the observation of the different tumor localizations. S-100 or HLA class II positive cells were found in the three different compartments of colorectal tumors: tumor epithelium, tumor stroma, and advancing tumor margin, but mainly present in tumor stroma and advancing tumor margin. S-100-positive tumor-infiltrating DCs in direct contact with tumor cells, i.e., in tumor epithelium, significantly correlated to the intraepithelial infiltration of CD4+ (p=0.02) and CD8+ (p=0.01) lymphocytes. High HLA class II+ cell infiltration in the tumor stroma correlated to a lower intraepithelial infiltration of CD8+ (p=0.02) lymphocytes. High intraepithelial infiltration of S-100-positive DCs suggested increased disease-free survival, but was not statistically significant, while high amounts of HLA class II+ cells in the tumor stroma correlated with an adverse survival outcome. Our results show that the infiltration of DCs in colorectal cancer, depending on both location and type of marker, is correlated with local immune interactions and patient prognosis, suggesting a central role for DCs in controlling local tumor immunity.

Amputation-sparing treatment by nature: "surgical" maggots revisited.

Maggots were used as adjunct treatment for infected wounds that showed no response to the classical approach of wound debridement and antibiotic therapy. We summarize findings for 11 patients with necrotic wounds who received treatment with "surgical" maggots (100-2900 applied in 3-10 changes of dressing) for 11-34 days, which apparently aided in tissue remodeling and cure, and describe 2 typical patients in detail.

Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation.

Although aquaporin 5 (AQP5) is the major water channel expressed in alveolar type I cells in the lung, its actual role in the lung is a matter of considerable speculation. By using immunohistochemical staining, we show that AQP5 expression in mouse lung is not restricted to type I cells, but is also detected in alveolar type II cells, and in tracheal and bronchial epithelium. Aqp5 knockout (Aqp5(-/-)) mice were used to analyze AQP5 function in pulmonary physiology. Compared with Aqp5(+/+) mice, Aqp5(-/-) mice show a significantly increased concentration-dependent bronchoconstriction to intravenously administered Ach, as shown by an increase in total lung resistance and a decrease in dynamic lung compliance (P < 0.05). Likewise, Penh, a measure of bronchoconstriction, was significantly enhanced in Aqp5(-/-) mice challenged with aerosolized methacholine (P < 0.05). The hyperreactivity to bronchoconstriction observed in the Aqp5(-/-) mice was not due to differences in tracheal smooth muscle contractility in isolated preparations or to altered levels of surfactant protein B. These data suggest a novel pathway by which AQP5 influences bronchoconstriction. This observation is of special interest because studies to identify genetic loci involved in airway hyperresponsiveness associated with asthma bracket genetic intervals on human chromosome 12q and mouse chromosome 15, which contain the Aqp5 gene.

Salivary acinar cells from aquaporin 5-deficient mice have decreased membrane water permeability and altered cell volume regulation.

Aquaporins (AQPs) are channel proteins that regulate the movement of water through the plasma membrane of secretory and absorptive cells in response to osmotic gradients. In the salivary gland, AQP5 is the major aquaporin expressed on the apical membrane of acinar cells. Previous studies have shown that the volume of saliva secreted by AQP5-deficient mice is decreased, indicating a role for AQP5 in saliva secretion; however, the mechanism by which AQP5 regulates water transport in salivary acinar cells remains to be determined. Here we show that the decreased salivary flow rate and increased tonicity of the saliva secreted by Aqp5(-)/- mice in response to pilocarpine stimulation are not caused by changes in whole body fluid homeostasis, indicated by similar blood gas and electrolyte concentrations in urine and blood in wild-type and AQP5-deficient mice. In contrast, the water permeability in parotid and sublingual acinar cells isolated from Aqp5(-)/- mice is decreased significantly. Water permeability decreased by 65% in parotid and 77% in sublingual acinar cells from Aqp5(-)/- mice in response to hypertonicity-induced cell shrinkage and hypotonicity-induced cell swelling. These data show that AQP5 is the major pathway for regulating the water permeability in acinar cells, a critical property of the plasma membrane which determines the flow rate and ionic composition of secreted saliva.