Postoperative Disease Recurrence Research Articles

Characterization of Crohn's disease patients in Egypt: Risk factors for postoperative recurrence (A cohort study)

BackgroundThe aim of study to identify the characterizations of Crohn's disease in Egyptian patients and to determine its predictors for postoperative recurrence. MethodsWe conducted a retrospective observational cohort study on 15 patients diagnosed as Crohn's disease with surgical interventions. Different characteristics of studied patients were analyzed to determine the risk factors for postoperative recurrence such as age at diagnosis, gender, smoking, main presenting symptom, Montreal classification, perianal disease, laboratory findings and protocol of management including surgical characteristics like age at operation, surgical indication, preoperative medication, surgical approach, and operative findings. ResultsNine of the studied patients (60%) suffered from clinical postoperative recurrence with mean duration of 23.5 ± 40.6 months. In comparison the demographic, clinical, operative, and medical treatment data between patients with postoperative recurrence of Crohn's disease and those without recurrence, age at diagnosis (mean age 42.9 years) and age at operation (mean 44.7 years) were found statistically significant in postoperative recurrence group (p-value = 0.001). According to Montreal classification of Crohn's disease, patients >40 years were significantly found in postoperative recurrence group, while patients between 17 and 40 years were significantly found in postoperative non-recurrence group (p-value=0.007) and ileal location of Crohn's disease was found significantly in postoperative recurrent group (p-value=0.044). Postoperative biological therapy significantly decreased the incidence of postoperative recurrence in the current study (p-value= 0.041). ConclusionsAge at diagnosis, age at operation, ileal location of Crohn's disease can significantly predict postoperative recurrence. Also, postoperative biological therapy can significantly decrease the incidence of postoperative recurrence.

Room for Improvement: The Trephination Procedure for Pediatric Patients with Pilonidal Disease

BackgroundPilonidal disease is common amongst adolescent males and females and often leads to recurrent symptoms and life-altering morbidity. The traditional surgical approach includes wide excision of the involved area and carries a high rate of postoperative morbidity. A minimally invasive surgical approach using trephines was described by Gips in 2008 and has since been widely adopted by many surgeons. The aim of this study was to explore outcomes of the trephination procedure for pediatric and adolescent patients by evaluating postoperative wound healing and disease recurrence. Materials and MethodsA retrospective cohort study for patients that underwent the trephination procedure as part of standard of care for the treatment of pilonidal disease from November 1, 2019-November 1, 2020 was performed. Patient demographics, presenting characteristics, and previous treatment history were identified. Outcome measures included healing time, recurrent disease, and need for reoperation. ResultsA total of 19 patients underwent the trephination procedure at a mean age of 16.4 years of age. An average of 3.8 pits were excised and there were no reported intraoperative complications. Following trephination, 26.3% of patients were healed at 30-day’s, with just over 40% showing complete healing by 6-months. The recurrence rate was 16.1% at 6-months and approximately 15% of patients required a second surgery. ConclusionEarly results for trephination at our institution show a high rate of healing complications and frequent reoperation. Future research is needed to establish the role of the trephination procedure in the context of defining the best practices for treating this challenging disease.

Quantifying the rate of recurrence of postoperative Crohn's disease with biological therapy. A meta-analysis.

Preventing the postoperative recurrence (POR) of Crohn's disease (CD) poses a significant challenge to clinicians. With the advent of biologics, various studies have observed a reduction of recurrence after surgery. Hence, we performed a systematic review and meta-analysis to identify the rate of POR at different time points in the era of biologic use. We performed a literature search using Medline and Embase databases for studies investigating biologics in preventing the POR of CD. Data were extracted, and a single-arm meta-analysis with generalized linear mixed model and Clopper-Pearson method for confidence interval (CI) was performed to identify endoscopic, clinical and surgical recurrence rates at 6 months and 1, 2 and 5 years postoperatively. Altogether 24 studies were included in the meta-analysis. The endoscopic, clinical and surgical POR rate with the use of anti-tumor necrosis factor (TNF)-α agents at 1 year was 21.72% (95% CI 16.28%-28.37%), 13.06% (95% CI 8.18%-18.92%) and 3.76% (95% CI 1.37%-9.91%), respectively. The 5-year recurrence rate was 84.21% (95% CI 72.35%-91.57%) and 17.49% (95% CI 9.17%-30.80%) for endoscopic and surgical recurrence, respectively. Subgroup analyses at 1 year for the type of anti-TNF-α agent or the timing of initiation after surgery showed no significant difference in endoscopic, clinical and surgical recurrence rates. Anti-TNF-α agents are effective at preventing clinical, endoscopic and surgical POR of CD. The timing of initiating biological therapy after surgery has no significant effect on the rate of POR. The efficacy of infliximab and adalimumab for postoperative recurrence prevention is similar.

A Magnetic Resonance Imaging Index to Predict Crohn’s Disease Postoperative Recurrence: The MONITOR Index

We developed and validated a magnetic resonance imaging-based index to predict Crohn's disease (CD) postoperative recurrence (POR). Patients with CD who underwent a postoperative evaluation for recurrence (with colonoscopy and MRI no longer than 105 days apart) were included between 2006 and 2016 in University Hospital of Nancy, France. MRI items with good levels of intra-rater and inter-rater agreement (Gwet's coefficient ≥0.5) were selected. The MRI in Crohn's Disease to Predict Postoperative Recurrence (MONITOR) index's performance was assessed in terms of the area under the receiver operating characteristic curve (AUROC) and accuracy, by considering the Rutgeerts score as the gold standard. The MONITOR index was validated with a bootstrap method and an independent cohort. Seventy-three MRI datasets were interpreted by 2 radiologists. Seven items (bowel wall thickness, contrast enhancement, T2 signal increase, diffusion-weighted signal increase, edema, ulcers, and the length of the diseased segment) had a Gwet's coefficient ≥0.5 and were significantly associated with the Rutgeerts score, leading to their inclusion in the MONITOR index. All the items had a weighting of 1, except the "ulcers" item weighting 2.5, reflecting the higher adjusted odds ratio. The AUROC [95% confidence interval] for the prediction of endoscopic POR (Rutgeerts score >i1) was 0.80 [0.70-0.90]. The optimal threshold was a MONITOR index ≥1, giving a sensitivity of 79%, a specificity of 55%, a predictive positive value of 68%, and a predictive negative value of 68%. The bootstrap validation gave an AUROC of 0.85 [0.73-0.97]. In the validation cohort, a MONITOR index ≥1 gave a sensitivity of 87%, a specificity of 75%, a predictive positive value of 84.6%, and a predictive negative value of 75%. The MONITOR index is an efficient, reliable, easy-to-apply tool that can be used in clinical practice to predict the POR of CD.

Diagnosis of postoperative recurrence of Crohn disease with MR-enterography: Value of diffusion-weighted imaging

PurposeTo compare the diagnostic capabilities of MR enterography (MRE) using contrast-enhanced (CE) sequences with those of MRE using diffusion-weighted (DW) imaging for the diagnosis of postoperative recurrence at the neo-terminal ileum and/or anastomosis after ileocolonic resection in patients with Crohn disease (CD), and to clarify the role of additional DW imaging to CE-MRE in this context. Material and methodsForty patients who underwent ileal resection for CD, and both endoscopy and MRE within the first year after surgery were included. There were 21 men and 19 women, with a mean age of 38 years±12 (SD) years (range: 18–67 years). MRE examinations were blindly analyzed independently by one senior (R1) and one junior (R2) radiologist for the presence of small bowel postoperative recurrence at the anastomotic site. During a first reading session, T2-, steady-state- and DW-MRE were reviewed (DW-MRE or set 1). During a separate distant session, T2-, steady-state- and CE-MRE were reviewed (CE-MRE or set 2). Lastly, all sequences were analyzed altogether (set 3). Performances of each reader for the diagnosis of postoperative recurrence were evaluated using endoscopic findings as the standard of reference (Rutgeerts score≥i2b). ResultsFifteen patients out of 40 (37.5%) had endoscopic postoperative recurrence at the anastomotic site. Sensitivity for the diagnosis of postoperative recurrence was 73% (95% CI: 51–96%) for R1 and 67% (95% CI: 43–91%) for R2 using set 1, and 80% (95% CI: 60–100%) for both readers using set 2. There was no significant differences in sensitivity between reading set 1 and reading set 2, for either R1 or R2 (R1, P> 0.99; R2, P=0.48). Specificity was 96% (95% CI: 88–100%) for both readers using set 1 or using set 2. Reading set 3 yielded an area under the ROC curve (AUC) of 0.93 (95% CI: 0.84–1) versus 0.89 (95% CI: 0.75–1) with set 1 (P=0.18) and versus 0.89 (95% CI: 0.78–1) with set 2 (P=0.21). No significant differences in AUC were found between set 1 or 2 and set 3 (P=0.18), nor between set 1 and 2 (P=0.76). Accuracies were 88% (95% CI: 74–95%) and 85% (95% CI: 71–93%) for DW-MRE for R1 and R2, respectively; 90% (95% CI: 77–96%) for CE-MRE for both readers; and 93% (95% CI: 80–97%) and 88% (95% CI: 74–95%) for R1 and R2 with set 3, respectively. ConclusionDW-MRE has diagnostic capabilities similar to those of CE-MRE for the diagnosis of postoperative recurrence of CD at the anastomotic site.

Comprehensive Transcriptomic Analysis Reveals Prognostic Value of an EMT-Related Gene Signature in Colorectal Cancer

Lymph node metastasis (LNM) is closely related to the postoperative recurrence of colorectal cancer (CRC), and greatly affects patient survival. Conducting Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA), we found that the epithelial-mesenchymal transition (EMT) signaling pathway is the signaling pathway most relevant to the process of LNM. An EMT-related gene signature was identified from a discovery dataset obtained 489 patients using LIMMA and LASSO Cox methods. Six external independent dataset analyses including a total of 1,045 CRC patients and stratification analysis showed that EMT-related gene signature could sort out those high- and low-risk CRC patients accurately. Functional analysis and loss-of-function exploration in vitro and in vivo indicated that the EMT-related-signature-associated coding genes might play functional roles in the sophisticated regulation of CRC proliferation and metastasis. Prognostic nomograms integrating the EMT-related gene signature and clinicopathological risk factors were constructed for use as numerical prediction tools to assess clinical prognosis and clinical decision-makings. The comprehensive transcriptomic analysis in this article highlights the prognostic value of an EMT-related gene signature for postoperative disease recurrence in CRC patients and reveals a potential prognostic and therapeutic biomarker for CRC.

Nutritional and Botanical Approaches for Inflammatory Bowel Disease

Nutritional and Botanical Approaches for Inflammatory Bowel Disease

DOP36 Non-invasive assessment of postoperative disease recurrence in Crohn’s Disease: A multicenter, prospective cohort study

Abstract Background Prevention of postoperative recurrence is a critical goal in Crohn’s disease (CD) management. Currently, postsurgical CD management and treatment are based on endoscopic monitoring performed within the first year after surgery. However, colonoscopy (CS) is an invasive and expensive procedure, unpleasant to patients. A non-invasive and patient friendly approach is required. Methods Consecutive CD patients who underwent ileo-cecal resection from July 2017 to January 2020 were prospectively enrolled in three Italian Centers and performed CS and bowel ultrasound (US) after six months from the surgery, in a blinded fashion. The patients also underwent complete clinical assessment and blood and stool samples were obtained for C-reactive protein (CRP), and fecal calprotectin (FC) measurements. The disease was considered clinically active if the Harvey–Bradshaw Index (HBI) was higher than 4. Uni- and multivariable analyses were used to assess the correlation between non-invasive parameters, including bowel US findings and FC values and endoscopic recurrence, defined by a Rutgeerts’s score (RS) > 2. Sensitivity, specificity, accuracy, PPV and NPV of bowel US parameters alone and in combination with FC in assessing endoscopic recurrence were calculated. Results Seventy patients were enrolled, 45 patients (64%) had an endoscopic recurrence (RS > 2) at 6 months. Thirteen out of 45 (29%) were symptomatic (HBI > 4). Bowel wall thickness (BWT), bowel wall flow (BWF, presence of vascular signals at color Doppler), the presence of mesenteric hypertrophy, the presence of limph-nodes and FC values significantly correlated with the endoscopic recurrence (p < 0.005). Independent predictors for endoscopic recurrence were BWT (for 1-mm increase: OR 2.63; 95% CI 1.136.12; p= 0.024), presence of lymph-nodes (OR 23.24; 95% CI 1.85291.15; p= 0.014) and FC > 50 µg/g (OR 11.86; 95% CI 2.60–54.09; p= 0.001). Sensitivity, specificity, accuracy, PPV and NPV of bowel US and/or FC are showed in Table 1. Table 1: Diagnostic accuracy of Bowel US and/or FC compared to CS in assessing endoscopic activity (CI 95%): per-patient analysis Conclusion Combined use of bowel US and FC is accurate in assessing endoscopic recurrence at 6 months in CD patients and represent a valid alternative to endoscopic assessment after surgery

Correlación entre la endoscopia y la ecografía intestinal para la evaluación de la recurrencia posquirúrgica de la enfermedad de Crohn

ObjectiveIntestinal ultrasound is considered to be a valid alternative for the evaluation of post-operative recurrence (POR) of Crohn's disease. The aim of this study is to assess the correlation between ultrasound and endoscopic findings. MethodsPatients with Crohn's disease were retrospectively recruited who had undergone ileocecal resection, and for whom a colonoscopy and intestinal ultrasound had been performed for the detection of POR. Recurrence was assessed using the Rutgeerts score (RS). The ultrasound findings analysed were bowel wall thickness (BWT), parietal hyperaemia using power Doppler, loss of layer pattern and mesenteric fat hypertrophy. ResultsA total of 31 patients were included, of which 15 (48.4%) had no POR (RS<2b) and 16 (51.6%) had POR (RS≥2b). A statistically significant association was identified between BWT and the presence of endoscopic recurrence (a mean of 2.75mm vs. 5.68mm, P>0.001). There was also a statistically significant difference in hyperaemia between the 2groups (P=0.03). For wall thickness, an area under the ROC curve (AUC) of 92.9% was obtained, and with a cut-off point of 3.4mm, a sensitivity of 100% and specificity of 86.6%. When comparing with the most frequent biomarkers (fecal calprotectin and serum CRP), a higher AUC was obtained for wall thickness (72.3% and 72.3% vs. 92.9%). ConclusionsIn our experience, ultrasound has high diagnostic efficacy in the detection of POR and can be considered a valid non-invasive alternative to endoscopy.

P03.03 MERMAID-1: A Phase III Study of Adjuvant Durvalumab plus Chemotherapy in Resected NSCLC Patients with MRD+ Post-Surgery

30% of non-small-cell lung cancer (NSCLC) patients present with surgically resectable disease at diagnosis. To reduce disease recurrence, adjuvant chemotherapy is standard of care (SoC) for patients with completely (R0) resected stage II/III NSCLC. However, 5-year disease-free survival (DFS) rates remain low (∼40%), with a 5-year absolute benefit of only 5.4% derived from chemotherapy (Pignon et al. JCO 2008;26:3552-9). Determining who will benefit from adjuvant chemotherapy remains challenging. Identifying minimal residual disease (MRD) through detection of circulating tumour (ct) DNA post-surgery could predict early disease recurrence. Durvalumab is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. In the phase III PACIFIC trial of patients with unresectable, stage III NSCLC without disease progression following radical platinum-based concurrent chemoradiotherapy, durvalumab improved progression-free survival (PFS) and overall survival (OS), demonstrating its efficacy in situations of residual disease. Further, initial data from POSEIDON showed durvalumab plus chemotherapy prolongs PFS versus chemotherapy in first line treatment of metastatic NSCLC. In the adjuvant setting (i.e. following complete tumour resection), this regimen could provide additional DFS benefit versus chemotherapy alone. MRD assessment could facilitate earlier, more selective adjuvant therapy for MRD+ patients, allowing for treatment intensification for this potentially biologically distinct disease, while minimising overtreatment of MRD– patients. MERMAID-1 will investigate the efficacy and safety of adjuvant durvalumab + SoC chemotherapy versus placebo + SoC chemotherapy in patients with completely resected stage II/III NSCLC, to assess the benefits of adjuvant therapy in patients with MRD+ status. MERMAID-1 (NCT04385368) is a phase III, parallel-arm, placebo-controlled, double-blind, multicentre study, conducted across 16 countries. Patients aged ≥18 years with histologically confirmed EGFR-/ALK- Wild-type, stage II/III NSCLC will enter the first screening period; a personalised MRD panel will be created. Before randomisation, and following assessment of MRD status post-surgery, patients will be further screened for full eligibility (no evidence of disease recurrence, WHO/ECOG performance status 0/1). Patients who have received prior adjuvant therapy or durvalumab, and those with mixed small cell and NSCLC histology or evidence of post-operative disease recurrence are ineligible. MRD status will be determined via ctDNA analysis of plasma samples, collected 3–4 weeks post-surgery, and based on personalised panels (comprised of ≤50 tumour-specific DNA variants) created by whole exome sequencing analysis of the patient’s resected tumour tissue. Approximately 332 patients will be randomised 1:1 (stratified by disease stage, MRD status, and PD-L1 expression) to durvalumab (1500 mg, intravenously) or placebo, plus concurrent SoC chemotherapy, once every three weeks (Q3W) for 12 weeks. Patients will continue with durvalumab monotherapy/placebo Q4W thereafter, until Week 48 or disease recurrence, whichever occurs first. Following a baseline radiological scan prior to randomisation, patients will be assessed Q12W until disease recurrence (per RECIST v1.1). The primary endpoint is DFS in the MRD+ analysis set (investigator-assessed). Secondary endpoints include DFS in the full analysis set (FAS; investigator-assessed); DFS in the MRD+ analysis set and FAS (blinded independent central review); OS in the MRD+ analysis set and FAS; and safety and tolerability, and patient-reported outcomes. adjuvant therapy, minimal residual disease, PD-L1

Von Willebrand factor antigen as a versatile preoperative marker in patients undergoing liver resection for hepatocellular carcinoma

Presenter: Patrick Starlinger MD | Mayo Clinic, Rochester Background: Risk evaluation in patients with hepatocellular carcinoma (HCC) prior to liver resection is an ongoing debate in the field, as long-term outcome is affected by an increased risk for LD and early disease recurrence. Currently available predictors are costly, not broadly available and lack predictive accuracy. Recently, vWF-Ag was established as a marker for postoperative LD. Due to its pleiotropic associations with components of HCC pathology vWF-Ag was further investigated in a variety of malignant diseases. This study aimed to compare routinely available parameters of risk assessment in HCC patients prior to liver resection and investigate the role of von Willebrand factor antigen (vWF-Ag) as a biomarker for postoperative liver dysfunction (LD), disease recurrence and long-term overall survival (OS). Methods: A total of 72 patients suffering from HCC was included out of a prospective trial cohort investigating the predictive potential of vWF-Ag for immediate outcome after liver resection in 223 patients (ClinicalTrials.gov-Identifier:NCT02118545). Patients clinical course was documented and they were followed up for disease recurrence and OS after discharge. Results: Upon logistic regression only vWF-Ag, volumentric assessment of future liver remnant (FLR) and measures of indocyanine green clearance (ICG-C) were able to predict patients risk for development of LD. In direct comparison using ROC-analysis, vWF-Ag was found to be comparable to parameters of ICG-C (area under the curve [AUC] = 0.828, vs 0.894 and 0.880) and more accurate than FLR (AUC = 0.756) and hepatic venous pressure gradient (HVPG, AUC = 0.590). Multivariable Cox-regression further revealed an independent association of vWF-Ag with disease free survival (odds ratio [OR] = 1.004, 95% confidence interval [CI] : 1.000-1.008). Ultimately, prediction of OS according to preoperative vWF-Ag was independent from development of postoperative LD, morbidity and disease recurrence. Given the clinical relevance to identify patients that might not benefit from liver resection and better served with other treatment options we defined a high risk cohort that developed LD in 55.6% of the cases (vs. 12.7% in vWF-AgLOW patients, p = 0.002) and had a 50% risk for postoperative mortality within the first postoperative year (vs. 11.7% in vWF-AgLOW patients, p = 0.006). Conclusion: Preopertive vWF-Ag is comparable to or more accurate than costly methods of preoperative risk evaluation, including volumetric estimation of FLR, ICG-C and HVPG measurement. In addition, preoperative vWF-Ag is associated with OS independent of postoperative outcome. The present data stresses the use of vWF-Ag as a broadly available routine laboratory parameter in preoperative risk evaluation for HCC patients and suggests that it might allow to personalize surgical strategy and treatment plan to the individual patient.

Impact of Clinically Relevant Postoperative Pancreatic Fistula on Pancreatic Ductal Adenocarcinoma Recurrence Rates

Purpose: Postoperative pancreatic fistula is a major complication after pancreatic surgery. Its effects on the immediate short-term outcome are well-known, however, data regarding the influence of clinically relevant postoperative pancreatic fistula on the recurrence rate of pancreatic ductal adenocarcinoma are still controversial. Herein we evaluate its impact on pancreatic ductal adenocarcinoma recurrence rates and on patients´ overall survival and disease-free survival. Methods: This is a retrospective analysis including all patients undergoing pancreaticoduodenectomy or distal pancreatectomy for pancreatic ductal adenocarcinoma at our center between 02/2012 and 12/2018. Clinically relevant postoperative pancreatic fistula was defined as grade B and C fistulas according to the International Study Group on Pancreatic Surgery (ISGPS). Results: 127 patients were included in the study. The median age was 67 years, 60 patients (47.2%) were female. 97 patients (76.4%) underwent pancreaticoduodenectomy and 30 (23.6%) a distal pancreatectomy. The overall incidence of clinically relevant postoperative pancreatic fistula was 8.6% (n = 11). Four occurred following pancreaticoduodenectomy and 7 after distal pancreatectomy (p = 0.004). After a median follow-up of 19 months (range 0 - 122) local and/or systemic recurrence occurred in 72 patients (56.7%). 23 (18.1%) experienced local, 38 (29.9%) systemic recurrence, and in 10 patients, the disease recurred both locally and systemically (7.9%). There was no association between clinically relevant postoperative pancreatic fistula recurrence of disease, independently of its localization (p = 0.772). Disease-free survival was 14 and 12 months, respectively, in patients without or with a clinically relevant postoperative pancreatic fistula (p = 0.250). Similarly, the occurrence of clinically relevant postoperative pancreatic fistula did not significantly influence the median overall survival (22.5 vs 16 months; p = 0.550). Conclusion: In our experience, clinically relevant postoperative pancreatic fistula does not have a significant oncologic impact in patients suffering from pancreatic ductal adenocarcinoma.

Aberrant differentiation of intestinal stem cells due to inflammation-induced mitochondrial dysfunction predicts postoperative recurrence of Crohn's disease.

Aberrant differentiation of intestinal stem cells due to inflammation-induced mitochondrial dysfunction predicts postoperative recurrence of Crohn's disease.

Potential clinical application of free-circulating DNA from blood in renal cancer

Early diagnosis of renal cancer carcinoma is a key determinant of patient survival. The asymptomatic disease course and lack of reliable diagnostic markers lead to the fact that more than 30 % renal cancer cases discovered at an advanced stage, when the prognosis is poor because kidney tumors are resistant to standard chemotherapy and radiation. More than 30 % of renal cancer carcinoma recur or metastasize after surgical treatment. Despite the implementation of novel targeted drugs and immune point inhibitors, the 5-year survival rate for metastatic renal cancer carcinoma remains dismal. Unsatisfactory result of renal cancer treatment may be caused by high inter- and intra-tumor heterogeneity and tumor evolution during therapy, as well as the lack of predictive and on-treatment monitoring biomarkers. Liquid biopsy test that utilizes free-circulating DNA (cfDNA) in the blood of patients, opens up new opportunities for managing patients with renal cancer. The diagnostic and predictive potential of these minimally invasive biomarkers has been demonstrated for various types of cancer. The use of highly sensitive methods of cfDNA analysis may allow early cancer detection and prediction of postoperative disease recurrence before dinical and radiographic progression. Serial cfDNA samples, that were collected before and during course of treatment, can provide information about the dynamic mutational changes in the volume of the entire tumor and metastases in real time, and the emergence of drug resistance during treatment. This information may be promising toolfor optimizing patient-specific therapeutic strategies. This review is focusing on the potential clinical application of cfDNA from blood in renal cancer.

T cells show preferential adhesion to enteric neural cells in culture and are close to neural cells in the myenteric ganglia of Crohn's patients

Plexitis in the proximal margin of intestinal resections are associated with post-operative recurrence of Crohn's disease. To understand their formation, in vitro analyzes were performed. T cells adhered preferentially to neuron and glial cells in mixed primary cultures of enteric nervous system and T cell activation increased their adhesion capacity. Higher number of T lymphocytes in close proximity to enteric glial cells was also observed in the myenteric ganglia of Crohn's patients as compared to control. These data show that close proximity between lymphocytes and enteric neural cells exists and may contribute to the formation of plexitis.

Patience is a virtue: Multiple preoperative visits are associated with decreased recurrence in pediatric pilonidal disease

Background/PurposeThis study aimed to compare preoperative management strategies for patients undergoing trephination for pilonidal disease and evaluate risk factors for recurrence. MethodsA retrospective review was performed of children undergoing index surgical treatment with trephination for pilonidal disease between September 2017 and April 2019. Intraoperative and postoperative management were standardized. Demographic and perioperative data were collected and analyzed. ResultsOne-hundred twenty patients were identified with a median follow-up time of 7.5 months (interquartile range 4.1–13.2 months). Overall, 24 (20%) patients had a postoperative recurrence of pilonidal disease. Patients with multiple preoperative surgery clinic visits were less likely to have recurrent disease compared to those seen only once preoperatively (11% vs 26%, p = 0.040). Compared to patients without recurrence, those who recurred went to the operating room sooner from the time of initial surgical consultation (32 days vs 54 days, p < 0.001). Perioperative antibiotics, history of acute infection, and prior drainage procedures were not risk factors for recurrence. ConclusionsMultiple preoperative clinic visits are associated with a lower recurrence rate in children undergoing trephination for pilonidal disease. An increased duration of preoperative medical management may be responsible for this finding. Prospective study is needed to confirm these findings and identify additional factors that influence recurrence. Type of StudyTreatment Study. Level of EvidenceIII (Retrospective Comparative).

A Novel Endoscopic Score for Postoperative Recurrence of Crohn's Disease: More Information Needed.

A Novel Endoscopic Score for Postoperative Recurrence of Crohn's Disease: More Information Needed.

Oncological impact of inflammatory biomarkers in elderly patients treated with radical cystectomy for urothelial bladder cancer

ABSTRACT Objective To evaluate the impact of preoperative markers of systemic inflammation on complications and oncological outcomes in patients aged ≥75 years treated with radical cystectomy (RC) for urothelial bladder cancer (UBC). Patients and methods The clinical data of 694 patients treated with open RC for UBC at our institution between January 2008 and December 2015 were retrospectively reviewed. Patients aged <75 years, with distant metastases, other-than-urothelial histological type, comorbidities that could affect the systemic inflammatory markers, and patients who received neoadjuvant chemotherapy were excluded. Multivariable regression models were built for the prediction of major postoperative surgical complications, disease recurrence, cancer-specific mortality (CSM), and overall mortality (OM). Results The median (interquartile range [IQR]) age at surgery was 79 (75–83) years. Major postoperative surgical complications were registered in 41.9% of the patients. The 5-year overall survival, cancer-specific survival and recurrence-free survival rates were 42.4% (95% confidence interval [CI] 34.7–49.9%), 70.3% (95% CI 62.3–76.9%), and 59.8% (95% CI 52.4–66.5), respectively. At multivariable analysis, higher levels of fibrinogen and a modified Glasgow Prognostic Score (mGPS) of 1 and 2 at baseline were independently associated with higher risk of major postoperative complications and of CSM. The inclusion of mGPS and fibrinogen to a standard multivariable model for recurrence and for CSM increased discrimination from 69.4% to 73.0% and from 71.3% to 73.9%, respectively. Preoperative neutrophil-to-lymphocyte ratio of >3 was independently associated with OM (hazard ratio 1.38, 95% CI 1.01–1.77; P = 0.01). Conclusions In a cohort of elderly patients with UBC treated with RC, fibrinogen and mGPS appeared to be the most relevant prognostic measurements and increased the accuracy of clinicopathological preoperative models to predict major postoperative complications, disease recurrence and mortality. Abbreviations ASA: American Society of Anesthesiologists; CCI: Charlson Comorbidity Index; CIS: carcinoma in situ; CRP: C-reactive protein; CSM: cancer-specific mortality; CSS: cancer-specific survival; ECOG PS: Eastern Cooperative Oncology Group Performance Status; HDL: high-density lipoprotein; (S)HR: (subdistribution) hazard ratio; LND: lymphadenectomy; LVI: lymphovascular invasion; mGPS: modified Glasgow Prognostic Score; NLR: neutrophil-to-lymphocyte ratio; NOC: non-organ-confined; OM: overall mortality; OR: odds ratio; OS: overall survival; RC: radical cystectomy; RNU: radical nephroureterectomy; UBC: urothelial bladder cancer; UTUC: upper urinary tract urothelial carcinoma

Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma.

High morbidity and mortality of cancer, especially colorectal cancer (CRC), in diabetic patients have been reported. In this study, we investigated the relationship between the presence of diabetes mellitus (blood hemoglobin A1C was 6.5% or higher at the time of diagnosis of CRC) and the progression and liver metastasis of CRC. Histopathological findings in the primary lesions, which were preferential to diabetes-complicated CRC (DM-CRC) and the liver metastasis, were also investigated. Of the 473 CRC patients who underwent curative surgical resection, 148 (31%) had diabetes. In DM-CRC cases, the stage was more advanced, with more cases in stage IV or postoperative disease recurrence. Histopathological findings correlated with liver metastasis in DM-CRC, including budding grade, perineural invasion, and myxomatous tumor stroma, and all were highly correlated with the stage. Additionally, myxomatous stroma showed the strongest correlation with liver metastasis in multivariate analysis. Myxomatous stroma in stage III cases correlated with liver recurrence. The myxomatous stroma was abundant in biglycan protein and contained numerous CD90-positive mesenchymal stem cells (MSCs). In human colon cancer cell line HT29, biglycan expression was induced by high sugar concentration, fatty acids, and insulin, and its contact co-culture with MSCs resulted in enhanced stemness and epithelial-mesenchymal transition phenotype. Thus, DM-CRC has higher malignant phenotypes compared to non-DM-CRC, and the involvement of diabetes-induced biglycan may act as a pathogenic factor.

Antitumor Necrosis Factor Agents to Treat Endoscopic Postoperative Recurrence of Crohn's Disease: A Nationwide Study With Propensity-Matched Score Analysis.

INTRODUCTION:Patients with Crohn's disease experiencing endoscopic postoperative recurrence (POR) may benefit from antitumor necrosis factor (TNF) agents but scarce data on this are available. Our aim was to assess the efficacy of anti-TNF in improving mucosal lesions in patients with endoscopic POR.METHODS:Multicenter, retrospective, study of patients with Crohn's disease who underwent therapy with anti-TNF agents for endoscopic POR (Rutgeerts score > i1). Treatment outcomes were assessed by the findings in the last ileocolonoscopy performed after anti-TNF therapy was initiated. Endoscopic improvement and remission were defined as any reduction in the baseline Rutgeerts score and by a Rutgeerts score < i2, respectively.RESULTS:A total of 179 patients were included, 83 were treated with infliximab and 96 with adalimumab. Median time on anti-TNF therapy at the last endoscopic assessment was 31 months (interquartile range, 13–54). Endoscopic improvement was observed in 61%, including 42% who achieved endoscopic remission. Concomitant use of thiopurines and treatment with infliximab were associated with endoscopic improvement (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.04–4.46; P = 0.03, and OR 2.34, 95% CI 1.18–4.62; P < 0.01, respectively) and endoscopic remission (OR 3.16, 95% CI 1.65–6.05; P < 0.01, and OR 2.01, 95% CI 1.05–3.88; P = 0.04, respectively) in the multivariable logistic regression analysis. These results were confirmed in a propensity-matched score analysis.DISCUSSION:In patients with endoscopic POR, anti-TNF agents improve mucosal lesions in almost two-thirds of the patients. In this setting, concomitant use of thiopurines and use of infliximab seem to be more effective in improving mucosal lesions.