Impact of Preoperative Time Intervals for Neoadjuvant Chemoradiotherapy on Short-term Postoperative Outcomes of Esophageal Cancer Surgery: A Population-based Study Using the Dutch Upper Gastrointestinal Cancer Audit (DUCA) Data.

OBJECTIVE: To clarify the impact of the preoperative time intervals on short-term postoperative and pathologic outcomes in patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. BACKGROUND: The impact of preoperative intervals on patients with esophageal cancer who received multimodality treatment remains unknown. METHODS: Patients (cT1-4aN0-3M0) treated with nCRT plus esophagectomy were included using the Dutch national DUCA database. Multivariate logistic regression was used to determine the effect of different time intervals upon short-term postoperative and pathologic outcomes: diagnosis-to-nCRT intervals (≤5, 5-8, and 8-12 weeks), nCRT-to-surgery intervals (5-11, 11-17, and >17 weeks) and total preoperative intervals (≤16, 16-25, and >25 weeks). RESULTS: Between 2010 and 2021, a total of 5052 patients were included. Compared with diagnosis-to-nCRT interval ≤5 weeks, the interval of 8 to 12 weeks was associated with a higher risk of overall complications ( P =0.049). Compared with nCRT-to-surgery interval of 5 to 11 weeks, the longer intervals (11-17 and >17 weeks) were associated with a higher risk of overall complications ( P =0.016; P <0.001) and anastomotic leakage ( P =0.004; P =0.030), but the interval >17 weeks was associated with lower risk of ypN+ ( P =0.021). The longer total preoperative intervals were not associated with the risk of 30-day mortality and complications compared with the interval ≤16 weeks, but the longer total preoperative interval (>25 weeks) was associated with higher ypT stage ( P =0.010) and lower pathologic complete response rate ( P =0.013). CONCLUSIONS: In patients with esophageal cancer undergoing nCRT and esophagectomy, prolonged preoperative time intervals may lead to higher morbidity and disease progression, and the causal relationship requires further confirmation.

Discontinuation of neoadjuvant therapy does not influence postoperative short-term outcomes in elderly patients (≥ 70 years) with resectable gastric cancer: a population-based study from the dutch upper gastrointestinal cancer audit (DUCA) data.

BACKGROUND: For the elderly patients with gastric cancer, it may be more challenging to tolerate complete neoadjuvant therapy (NAT). The impact of discontinued NAT on the surgical safety and pathological outcomes of elderly patients with poor tolerance remains poorly understood. METHODS: Gastric cancer patients received gastrectomy with curative intent from the Dutch upper GI cancer audit (DUCA) database were included in this study. The independent association of age with not initiating and discontinuation of NAT was assessed with restricted cubic splines (RCS). According to the RCS results, age ≥ 70 years was defined as elderly. Short-term postoperative outcomes and pathological results were compared between elderly patients who completed and discontinued NAT. RESULTS: Between 2011- 2021, total of 3049 patients were included. The risk of not initiating NAT increased from 70 years. In 1954 (64%) patients receiving NAT, the risk of discontinuation increased from 55 years, reaching the peak around 74 years. In the elderly, discontinued NAT was not independently associated with worse 30-day mortality, overall complications, anastomotic leakage, re-intervention, and pathologic complete response, but was associated with a higher risk of R1/2 resection (p-value = 0.001), higher ypT stage (p-value = 0.004), ypN + (p-value = 0.008), and non-response ( p-value = 0.012). CONCLUSION: A decreased utilization of NAT has been observed in Dutch gastric cancer patients from 70 years due to old age considerations, possibly because of their high risk of discontinuation. Increasing the utilization of NAT may not adversely impact the surgical safety of gastric cancer population ≥ 70 years and may contribute to better pathological results.

Safety and short-term outcomes of a modified valvuloplastic esophagogastrostomy versus gastric tube anastomosis after laparoscopy-assisted proximal gastrectomy: a retrospective cohort study.

BACKGROUND: There is no optimal reconstruction method after proximal gastrectomy. The valvuloplastic esophagogastrostomy can reduce postoperative reflux esophagitis, but it is technically complex with a long operation time. The gastric tube anastomosis is technically simple, but the incidences of reflux esophagitis and anastomotic stricture are higher. METHODS: We have devised a modified valvuloplastic esophagogastrostomy after laparoscopy-assisted proximal gastrectomy (LAPG), the arch-bridge anastomosis. After reviewing our prospectively maintained gastric cancer database, 43 patients who underwent LAPG from November 2021 to April 2023 were included in this cohort study, with 25 patients received the arch-bridge anastomosis and 18 patients received gastric tube anastomosis. The short-term outcomes were compared between the two groups to evaluate the efficacy of the arch-bridge anastomosis. Reporting was consistent with the STROCSS 2021 guideline. RESULTS: The median operation time was 180 min in the arch-bridge group, significantly shorter than the gastric tube group (p = 0.003). In the arch-bridge group, none of the 25 patients experienced anastomotic leakage, while one patient (4%) experienced anastomotic stricture requiring endoscopic balloon dilation. The postoperative length of stay was shorter in the arch-bridge group (9 vs. 11, p = 0.034). None of the patients in the arch-bridge group experienced gastroesophageal reflux and used proton pump inhibitor (PPI), while four (22.2%) patients in the gastric tube group used PPI (p = 0.025). The incidence of reflux esophagitis (Los Angeles grade B or more severe) by endoscopy was lower in the arch-bridge group (0% vs. 25.0%). CONCLUSION: The arch-bridge anastomosis is a safe, time-saving, and feasible reconstruction method. It can reduce postoperative reflux and anastomotic stricture incidences in a selected cohort of patients undergoing laparoscopy-assisted proximal gastrectomy.

Evaluation of Treatment Strategies and Survival of Patients with cT4bM0 Esophageal Cancer: A Nationwide Cohort Study.

INTRODUCTION: The optimal therapeutic strategy for patients with cT4bM0 esophageal cancer is controversial and varies internationally. This study aimed to describe treatment and survival of patients with cT4bM0 esophageal cancer in the Netherlands. METHODS: Patients staged with cT4bM0 esophageal cancer who were registered in the Netherlands Cancer Registry (NCR) were included. All patients were categorized by the treatment modality received. The Kaplan-Meier method was used to estimate the overall survival of them. RESULTS: Between 2015 and 2020, 286 patients with cT4bM0 esophageal cancer were included. Treatment consisted of preoperative chemoradiotherapy/chemotherapy followed by surgery (8%), chemoradiotherapy alone (35%), chemotherapy alone (6%), radiotherapy alone (19%), and best supportive care (32%). The median follow-up was 28.1 months. The 1-, 3-, and 5-year survival rates of each group were 82%, 58%, 49% for preoperative therapy plus surgery; 53%, 27%, 16% for chemoradiotherapy only; 13%, 0%, 0% for chemotherapy only; 13%, 0%, 0% for radiotherapy only; and 5%, 0%, 0% for best supportive care. CONCLUSION: In a selected group of patients, preoperative therapy followed by esophagectomy may lead to improved survival, which is comparable to patients with <cT4bM0 tumors. Therefore, reevaluation following chemo(radio)therapy is recommended in these patients to evaluate the possibility of additional surgical resection.

Genomic characterization of peritoneal lavage cytology-positive gastric cancer.

Objective: Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1 and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer. Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31 matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer. Results: Least absolute shrinkage and selection operator (LASSO) algorithm identified 43 cytology-positive marker genes, while MutSigCV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology (CY0). Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1 and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

Early Diagnosis of Anastomotic Leakage After Gastric Cancer Surgery Via Analysis of Inflammatory Factors in Abdominal Drainage.

BACKGROUND: Anastomotic leakage (AL) is the most serious postoperative complication for patients with gastric cancer. We aim to develop clinically tools to detect AL in the early phase by analysis of the inflammatory factors (IFs) in abdominal drainage. METHODS: We prospectively included 326 patients to establish two independent cohorts, and the concentration of IFs within abdominal drainage was detected. In the primary cohort, an IF-based AL prediction model was constructed using the least absolute shrinkage and selection operator (LASSO) regression. The predictive value of the model was later validated via the validation cohort. RESULTS: Analyzing the IFs with LASSO regression, we developed an Anastomotic Score system on postoperative Day 3 (AScore-POD3), which yielded high diagnostic efficacy in the primary cohort (the area under the curve (AUC) = 0.87). The predictive value of AScore-POD3 was validated in the validation cohort, and its AUC was 0.83. We further built an AScore-POD3 based nomogram by combining the AScore-POD3 system with other clinical risk factors of AL. The C-index of the nomogram was 0.93 in the primary cohort and 0.82 in the validation cohort. CONCLUSIONS: Our study suggests that AL can be early diagnosed after gastric cancer surgery by measuring drainage IFs.

Optimized tools and timing of response reassessment after neoadjuvant chemoradiation in rectal cancer.

PURPOSE: Reassessment tools of response to long-course neoadjuvant chemoradiation treatment (nCRT) in patients with locally advanced rectal cancer (LARC) are important in predicting complete response (CR) and thus deciding whether a wait-and-watch strategy can be implemented in these patients. Choosing which routine reassessment tools are optimal and when to use them is still unclear and will be researched in the study. METHODS: Altogether, 250 patients with LARC who received nCRT from 2013 to 2021 and were followed up were retrospectively reviewed. Common reassessment tools of response included digital rectal examination (DRE), clinical examination and symptoms, endoscopy, biopsy, magnetic resonance imaging (MRI), and blood biomarkers. RESULTS: Overall, 27.20% (68/250) patients had a complete response and 72.80% (182/250) did not. The combination of MRI, endoscopy, and biopsy showed the best performance in terms of accuracy of 74% and area under the curve (AUC, 0.714, 95% CI 0.546-0.882). Reassessing through DRE and presence of symptoms failed to improve the efficacy of response reassessment. After 100 days, biopsy as an assessment tool would obtain a substantial rise in accuracy from 51.28 to 100% (p = 0.003). CONCLUSION: The combination of MRI, endoscopy, and biopsy is suitable as the reassessment tool of response for applying a wait-and-watch strategy after long-course nCRT in patients with LARC. The accuracy of biopsy as reassessment tools would be improved if they were used over 100 days after nCRT in patients with rectal cancer.

Omitting nasogastric tube placement after gastrectomy does not enhance postoperative recovery: a propensity score matched analysis.

PURPOSE: Enhanced recovery after surgery (ERAS) program has become the main trend in gastrointestinal surgery. This study aims to investigate factors influencing the decision-making of nasogastric tube (NGT) placement and its safety and efficacy after gastrectomy. METHODS: We analyzed our prospectively maintained database including 287 patients who underwent elective gastrectomy in our department from January 1 to December 31, 2017. All cases were divided into two groups, namely, the no-NGT group and the NGT group. Logistic regression was used to analyze factors that affected the decision of NGT placement, and propensity score matching (PSM) was later applied to balance those factors for the analysis of safety outcomes between groups. RESULTS: Multivariate analysis showed resection range (p = 0.004, proximal gastrectomy: OR = 4.555, 95%CI = 1.392-14.905, p = 0.016; total gastrectomy: OR = 1.990, 95%CI = 1.205-3.287, p = 0.009) was the only independent risk factor of NGT placement. NGT was omitted in the majority (58.8%) of distal gastrectomy but only in 42.5% and 25% in total and proximal gastrectomy. After PSM, we found no significant differences between patients with or without NGT in postoperative hospital stay, time to first flatus and defecation, time to fluid and semi-fluid diet, rate of reinsertion, or hospitalization expenditure (p > 0.05, respectively). The incidence of postoperative complications in the two groups were 21.7% and 23.5%, respectively (p = 0.753), and the incidence of major complications was 7.0% and 9.6% (p = 0.472). CONCLUSION: The decision-making of NGT placement is mainly influenced by the resection range. Omitting NGT is a safe approach in all types of gastrectomy but was not able to enhance the recovery in our practice.

Different prognostic implication of ypTNM stage and pTNM stage for gastric cancer: a propensity score-matched analysis.

BACKGROUND: Pathological stage is considered as the best prognosis indicator for gastric cancer. With the increasing use of neoadjuvant chemotherapy (NACT), the latest TNM staging included a new pathological stage of ypTNM for patients with NACT. However, no study has investigated if ypTNM stage has the same prognostic implication as pTNM stage for gastric cancer. METHODS: We retrospectively selected eligible patients within a prospectively maintained database containing all patients treated with gastric cancer in Peking University Cancer Hospital from 2007 to 2015 using overall survival as the outcome. Patients using ypTNM and pTNM were 1:1 matched by propensity scores (PS) calculated from a model containing variables associated with ypTNM use or survival. Overall survival was compared by unconditional Cox regression. Conventional multivariate analysis was conducted to corroborate PS matching results. RESULTS: 1441 patients were included in the analysis with a median follow-up of 37 months (range = 2-106). The matched sample contained 756 patients. After PS matching, patients with specific ypTNM stage were 1.34 (95%CI = 1.05-1.72, P = 0.019) times more likely to die than patients with the same pTNM stage. Similar to the results of PS matching, multivariate Cox regression yielded a hazard ratio (HR) of 1.35 (95%CI = 1.09-1.67, P = 0.006). Subgroup analysis indicated this survival difference between ypTNM and pTNM stage varied by the specific TNM stage of patients. The HR was 3.44 (95%CI = 1.06-11.18, P = 0.040) and 1.28 (95%CI = 1.00-1.62, P = 0.048) for patients in stage I and III, respectively; whereas for stage II patients, no significant difference was observed (HR = 1.37, 95%CI = 0.78-2.38, P = 0.27). CONCLUSION: Gastric cancer patients with specific ypTNM stage had worse prognosis compared to those at the same stage defined by pTNM.

Impact of postoperative major complications on long-term survival after radical resection of gastric cancer.

BACKGROUND: This study was designed to evaluate the impact of postoperative major complications on long-term survival following curative gastrectomy. METHODS: This retrospective study included 239 patients with gastric cancer undergoing gastrectomy at the Beijing Cancer Hospital from February 2012 to January 2013. Survival curves were compared between patients with major complications (mC group) and those without major complications (NmC group). Multivariate analysis was conducted to identify independent prognostic factors. RESULTS: Postoperative complication and mortality rates were 24.7 and 0.8%, respectively. The severity of complications was graded in accordance with the Clavien-Dindo classification. The incidence of minor complications (grades I-II) and major complications (grades III-V) was 9.2 and 15.5%, respectively. The 3-year overall survival (OS) and disease-free survival (DFS) rates were better in the NmC group than in the mC group (p = 0.014, p = 0.013). Multivariate analysis identified major complications as an independent prognostic factor for OS and DFS. After stratification by pathological stage, this trend was also observed in stage II patients. CONCLUSIONS: Postoperative major complications adversely affect OS and DFS. The prevention and early diagnosis of complications are essential to minimize the negative effects of complications on surgical safety and long-term patient survival.

Non-Cross-Linked Collagen Mesh Performs Best in a Physiologic, Noncontaminated Rat Model.

BACKGROUND: In laparoscopic incisional hernia repair, direct contact between the prosthesis and abdominal viscera is inevitable and may lead to adhesions. Despite the large variety of mesh prosthesis, little is known about their in vivo behavior. Biological meshes are considered to have many advantages, but due to their price they are rarely used. A rat model was used to assess biological and conventional synthetic meshes on their in vivo characteristics. DESIGN: One-hundred twenty male Wistar rats were randomized into five groups of 24 rats. A mesh was implanted intraperitoneally and fixated with nonresorbable sutures. The following five meshes were implanted: Parietene (polypropylene), Permacol (cross-linked porcine acellular dermal matrix), Strattice (non-cross-linked porcine acellular dermal matrix), XCM Biologic (non-cross-linked porcine acellular dermal matrix), and Omyra Mesh (condensed polytetrafluoroethylene). The rats were sacrificed after 30, 90, or 180 days. Incorporation, shrinkage, adhesions, abscess formation, and histology were assessed for all meshes. RESULTS: All animals thrived postoperatively. After 180 days, Permacol, Parietene, and Omyra Mesh had a significantly better incorporation than Strattice ( P = .001, P = .019, and P = .037 respectively). After 180 days, Strattice had significantly fewer adhesions on the surface of the mesh than Parietene ( P < .001), Omyra Mesh ( P = .011), and Permacol ( P = .027). After 30 days, Permacol had significantly stronger adhesions than Strattice ( P = .030). However, this difference was not significant anymore after 180 days. After 180 days, there was significantly less shrinkage in Permacol than in Strattice ( P = .001) and Omyra Mesh ( P = .050). CONCLUSION: Based on incorporation, adhesions, mesh shrinkage, and histologic parameters, Strattice performed best in this experimental rat model.

ypTNM staging after neoadjuvant chemotherapy in the Chinese gastric cancer population: an evaluation on the prognostic value of the AJCC eighth edition cancer staging system.

BACKGROUND: This study aims to evaluate the new ypTNM staging system in Chinese gastric cancer patients. METHODS: We conducted retrospective survival and regression analyses using a database of gastric cancer patients who underwent neoadjuvant chemotherapy at the Peking University Cancer Hospital and Institute from January 2007 to January 2015. RESULTS: A total of 473 patients were included in the study with 28 pathological complete response (pCR) cases, 3 ypT0N1 cases, 65 stage I cases, 126 stage II cases, and 251 stage III cases. The pCR cases had similar survival to stage I patients (p > 0.05). The 3-year disease-free survival (DFS) and 5-year overall survival (OS) rates of stage I, II and III patients were significantly different (3-year DFS: 89.0, 75.5, and 39.6%, p < 0.001; 5-year OS: 89.6, 65.5, and 36.5%, p = 0.001). Both ypT and ypN are independent predictors of patient survival, while further log-rank tests showed that the ypN stage is of better prognostic value than ypT. Subgrouping analysis revealed that stage III patients of ypT4b and ypN3 had worse survival compared to the rest of stage III cases (p < 0.001). The c-index values of the ypTNM stage and modified ypTNM stage (stage III divided into IIIa and IIIb) were 0.657 and 0.708, respectively (p < 0.001). CONCLUSIONS: Our data showed significant differences in survival among gastric cancer patients at different ypTNM stages, indicating its prognostic value in the Chinese population. Further detailed analyses may facilitate the subgrouping of each stage to allow for a more accurate evaluation of disease prognosis in gastric cancer patients.

Pilot Study: Detection of Gastric Cancer From Exhaled Air Analyzed With an Electronic Nose in Chinese Patients.

The aim of this pilot study is to investigate the ability of an electronic nose (e-nose) to distinguish malignant gastric histology from healthy controls in exhaled breath. In a period of 3 weeks, all preoperative gastric carcinoma (GC) patients (n = 16) in the Beijing Oncology Hospital were asked to participate in the study. The control group (n = 28) consisted of family members screened by endoscopy and healthy volunteers. The e-nose consists of 3 sensors with which volatile organic compounds in the exhaled air react. Real-time analysis takes place within the e-nose, and binary data are exported and interpreted by an artificial neuronal network. This is a self-learning computational system. The inclusion rate of the study was 100%. Baseline characteristics differed significantly only for age: the average age of the patient group was 57 years and that of the healthy control group 37 years ( P value = .000). Weight loss was the only significant different symptom ( P value = .040). A total of 16 patients and 28 controls were included; 13 proved to be true positive and 20 proved to be true negative. The receiver operating characteristic curve showed a sensitivity of 81% and a specificity of 71%, with an accuracy of 75%. These results give a positive predictive value of 62% and a negative predictive value of 87%. This pilot study shows that the e-nose has the capability of diagnosing GC based on exhaled air, with promising predictive values for a screening purpose.

Reinforcement of the colon anastomosis with cyanoacrylate glue: a porcine model.

BACKGROUND: Previous experimental studies on cyanoacrylate (CA) glue for the prevention of colorectal anastomotic leakage (AL) have shown promising results. The aim of this study was to investigate the effect of CA in prevention of leakage in a porcine model of ischemic colorectal AL. METHODS: Twenty-four animals were divided into four groups of six: (1)ischemic anastomosis with sufficient suture (ISCH), (2)ischemic anastomosis with sufficient suture and CA reinforcement (CA-ISCH), (3)ischemic anastomosis with insufficient suture (ISCH-AI), and (4)ischemic anastomosis with insufficient suture and CA reinforcement (CA-ISCH-AI). In CA groups, N-butyl-2-cyanoacrylate was applied between the colon ends. Anastomotic bursting pressure, abscess formation, and adhesion formation were evaluated on postoperative day 7. Tissue samples were obtained for histologic evaluation of foreign body reaction. RESULTS: The AL rate was 4 of 6 (67%) in the ISCH-AI group compared with none in the other three groups. The ISCH and ISCH-AI groups had significantly higher AL scores compared with the CA groups. The mean anastomotic bursting pressure was 167 ± 54 mm Hg in the ISCH-group versus 213 ± 43 mm Hg in the CA-ISCH-group (P = nonsignificant) and 145 ± 102 mm Hg in the ISCH-AI group versus 187 ± 19 mm Hg in the CA-ISCH-AI group (P = nonsignificant). The average adhesion score was significantly higher in the ISCH group than in the CA-ISCH group (4.2 ± 1.3 versus 1.7 ± 0.82; P = 0.019). Stricture of the anastomosis occurred only in the non-CA groups (3/12, 25%). CONCLUSIONS: Anastomotic reinforcement with CA is effective and safe to prevent leakage in a high-risk colorectal anastomosis in a porcine model.

Nicotine chewing gum for the prevention of postoperative ileus after colorectal surgery: a multicenter, double-blind, randomised, controlled pilot study.

PURPOSE: When postoperative ileus is not resolved after 5 days or recurs after resolution, prolonged POI (PPOI) is diagnosed. PPOI increases discomfort, morbidity and hospitalisation length, and is mainly caused by an inflammatory response following intestinal manipulation. This response can be weakened by targeting the cholinergic anti-inflammatory pathway, with nicotine as essential regulator. Chewing gum, already known to stimulate gastrointestinal motility itself, combined with nicotine is hypothesised to improve gastrointestinal recovery and prevent PPOI. This pilot study is the first to assess efficacy and safety of nicotine gum in colorectal surgery. METHODS: Patients undergoing elective oncological colorectal surgery were enrolled in this double-blind, parallel-group, controlled trial and randomly assigned to a treatment protocol with normal or nicotine gum (2 mg). Patient reported outcomes (PROMS), clinical characteristics and blood samples were collected. Primary endpoint was defined as time to first passage of faeces and toleration of solid food for at least 24 h. RESULTS: In total, 40 patients were enrolled (20 vs. 20). In both groups, six patients developed PPOI. Time to primary endpoint (4.50 [3.00-7.25] vs. 3.50 days [3.00-4.25], p = 0.398) and length of stay (5.50 [4.00-8.50] vs. 4.50 days [4.00-6.00], p = 0.738) did not differ significantly between normal and nicotine gum. There were no differences in PROMS, inflammatory parameters and postoperative complications. CONCLUSIONS: We proved nicotine gum to be safe but ineffective in improving gastrointestinal recovery and prevention of PPOI after colorectal surgery. Other dosages and administration routes of nicotine should be tested in future research.

Impact of tissue adhesives on the prevention of anastomotic leakage of colonic anastomoses: an in vivo study.

BACKGROUND: Tissue adhesives (TA) may be useful to strengthen colorectal anastomoses, thereby preventing anastomotic leakage (AL). Previous studies have identified cyanoacrylate (CA) TAs as the most promising colonic anastomotic sealants. This study investigates the protective effects of sealing colonic anastomoses with various CAs. MATERIALS AND METHODS: Fifty-five Wistar rats underwent laparotomy and transection of the proximal colon. An anastomosis was created with 4 interrupted sutures followed by either application of Histoacryl Flexible, Omnex, Glubran 2, or no TA seal. An additional control group was included with a 12-suture anastomosis and no TA seal. After 7 days, the rats were sacrificed and scored for the presence of AL as the main outcome. Secondary outcomes were the occurrence of bowel obstruction, adhesions, and anastomotic bursting pressure. Histological evaluation was performed. RESULTS: The highest AL rate was found in the Glubran 2 group (7/11), followed by the 4-sutures group without TA (5/11), and the Omnex group (5/11). Histoacryl Flexible showed the lowest AL rate (2/11). In the control group, only one rat showed signs of AL. Histologically, the highest influx of inflammatory cells was found in the 4-suture group without TA and for Omnex and Glubran 2. Histoacryl Flexible caused more mature collagen deposition when compared to the other TA groups. CONCLUSIONS: Histoacryl Flexible showed the lowest leakage rate compared to the other TA groups and to the 4-suture control group. Glubran 2 showed the highest AL rate and a high inflammatory response. Histoacryl Flexible was associated with the presence of more mature collagen and seems to promote anastomotic healing.

Is the intraoperative air leak test effective in the prevention of colorectal anastomotic leakage? A systematic review and meta-analysis.

OBJECTIVE: The intra-operative air leak test (ALT) is a common intraoperative test used to identify mechanically insufficient anastomosis. This meta-analysis aims to determine whether ALT aids to the reduction of postoperative colorectal anastomotic leakage (CAL). METHODS: A literature search was performed to select studies in acknowledged databases. Full text articles targeting ALT during colorectal surgery were included. Quality assessment, risk of bias, and the level-of-evidence of the inclusions were evaluated. ALT methodology, ALT(+) (i.e., leak observed during the test) rate, and postoperative CAL rate of the included studies were subsequently analyzed. RESULTS: Twenty studies were included for analysis, in which we found substantial risks of bias. A lower CAL rate was observed in patients who underwent ALT than those did not; however, the difference was not significant (p = 0.15). The intraoperative ALT(+) rate greatly varied among the included studies from 1.5 to 24.7 %. ALT(+) patients possessed a significantly higher CAL rate than the ALT(-) patients (11.4 vs. 4.2 %, p < 0.001). CONCLUSIONS: Based on the available evidence, performing an ALT with the reported methodology has not significantly reduced the clinical CAL rate but remains necessary due to a higher risk of CAL in ALT(+) cases. Unfortunately, additional repairs under current methods may not effectively decrease this risk. Results of this review urge a standardization of ALT methodology and effective methods to repair ALT(+) anastomoses.

Postoperative Hemodynamic Index Measurement With Miniaturized Dynamic Light Scattering Predicts Colorectal Anastomotic Healing.

INTRODUCTION: Perioperative bowel perfusion (local hemodynamic index [LHI]) was measured with a miniaturized dynamic light scattering (mDLS) device, aiming to determine whether anastomotic perfusion correlates with the anastomotic healing process and whether LHI measurement assists in the detection of anastomotic leakage (AL) in colorectal surgery. METHODS: A partial colectomy was performed in 21 male Wistar rats. Colonic and anastomotic LHIs were recorded during operation. On postoperative day (POD) 3, the rats were examined for AL manifestations. Anastomotic LHI was recorded before determining the anastomotic bursting pressure (ABP). The postoperative LHI measurements were repeated in 15 other rats with experimental colitis. Clinical manifestations and anastomotic LHI were also determined on POD3. Diagnostic value of LHI measurement was analyzed with the combined data from both experiments. RESULTS: Intraoperative LHI measurement showed no correlation with the ABP on POD3. Postoperative anastomotic LHI on POD3 was significantly correlated with ABP in the normal rats (R(2) = 0.52; P < .001) and in the rats with colitis (R(2) = 0.63; P = .0012). Anastomotic LHI on POD3 had high accuracy for identifying ABP <50 mm Hg (Area under the curve = 0.86; standard error = 0.065; P < .001). A cutoff point of 1236 yielded a sensitivity of 100% and a specificity of 65%. On POD3, rats with LHIs <1236 had significantly higher dehiscence rates (40% vs 0%), more weight loss, higher abscess severity, and lower ABPs (P < .05); worse anastomotic inflammation and collagen deposition were also found in the histological examination. CONCLUSION: Our data suggest that postoperative evaluation of anastomotic microcirculation with the mDLS device assists in the detection of AL in colorectal surgery.

Mechanical strength and rheological properties of tissue adhesives with regard to colorectal anastomosis: an ex vivo study.

OBJECTIVE: To compare mechanical strength and rheology of existing tissue adhesives in a clinically relevant test setup with regard to colorectal anastomosis. BACKGROUND: Little is known on the mechanical strength of tissue adhesives directly after application. Furthermore, rheological profiling may be important in understanding mechanical performance and explaining differences between adhesives. This study provides new data on the mechanical strength and rheology of a comprehensive list of tissue adhesives with regard to colorectal adhesiveness. METHODS: Twelve surgical tissue adhesives were included: 4 cyanoacrylate adhesives (CA), 2 fibrin glues (FG), 3 polyethylene glycol (PEG) adhesives, and 3 albumin-based (AB) adhesives. Tubular rat colonic segments were glued together. Tensile (T), shear (S), and peel (P) strength were measured. Shear storage (G') and shear loss (G″) moduli were also evaluated. RESULTS: CA adhesives were stronger than AB (T: P = 0.017; S: P = 0.064; P: P < 0.001), which, in turn, were stronger than PEG (T: P < 0.001; S: P < 0.001; P: P = 0.018). PEG were stronger than FG for shear (P = 0.013) and comparable for tensile and peel strength (P > 0.05). Within-group variation was smallest for CA. Mechanical strength correlated strongly between performed tests. Rheological properties (G' and G″) correlated strongly with mechanical strength for all adhesives combined. CONCLUSIONS: CA adhesives are the strongest and most homogenous group in terms of mechanical strength. Hydrogels (FG, AB) are heterogeneous, with lower mechanical strength than CA. FG are mechanically the weakest adhesives. Rheological profiles correlate to mechanical strength and may be useful for predicting mechanical performance.

Clinical endpoint, early detection, and differential diagnosis of postoperative ileus: a systematic review of the literature.

BACKGROUND: This systematic review summarizes evidence regarding clinical endpoints, early detection, and differential diagnosis of postoperative ileus (POI). METHODS: Using MEDLINE, EMBASE, Cochrane, and Web-of-Science, we identified 2,084 articles. Risk of bias and level of evidence (LOE) of the included articles were determined, and relevant results were summarized. RESULTS: Eleven articles were included, most of which with substantial risks of bias. Bowel motility studies revealed that defecation together with solid food tolerance is the most representative clinical endpoint of POI (LOE: 2b); other clinical signs (e.g. bowel sounds, passage of flatus) did not correlate with a full recovery of bowel motility. Inflammatory parameters including interleukin (IL)-6, IL-1, and TNF-α might assist in an early detection of prolonged POI (LOE: 4). Clinical manifestations (e.g. nausea, vomiting, abdominal distension, bowel sounds, flatus) and X-ray examinations provided limited aid to the differential diagnosis of POI, while CT with Gastrografin had the best specificity and sensitivity (both 100%; LOE: 1c). CONCLUSIONS: Postoperative defecation together with tolerance of solid food intake seems to be the best clinical endpoint of POI. CT has the best differential diagnostic value between POI and other complications. Prospective studies with a high LOE are in great need.