The liver-first approach for synchronous colorectal liver metastases: A systematic review and meta-analysis of completion rates and effects on survival

Background: Patients presenting with synchronous colorectal liver metastases are increasinglybeing considered for a curative treatment, and the liver-first approach is gaining popularity in thiscontext. However, little is known about the completion rates of the liver-first approach and itseffects on survival.Methods:A systematic review and meta-analysis of liver-first strategy for colorectal liver metastasis.The primary outcome was an assessment of the completion rates of the liver-first approach.Secondary outcomes included overall survival, causes of non-completion, and clinicopathologicdata.Results: Seventeen articles were amenable for inclusion and the total study population was 1041.The median completion rate for the total population was 80% (range 20–100). The median overallsurvival for the completion and non-completion groups was 45 (range 12–69) months and 13 (range10.5–25) months, respectively. Metadata showed a significant survival benefit for the completiongroup, with a univariate hazard ratio of 12.0 (95% confidence interval, range 5.7–24.4). The majorcause of non-completion (76%) was liver disease progression before resection of the primarytumor. Pearson tests showed significant negative correlation between median number of lesionsand median size of the largest metastasis and completion rate.Conclusions: The liver-first approach offers a complete resection to most patients enrolled, withan overall survival benefit when completion can be assured. One-fifth fails to return to intendedoncologic therapy and the major cause is interim metastatic progression, most often in the liver.Risk of non-completion is related to a higher number of lesions and large metastases. The majorityof studies stem from primar

The liver-first approach for synchronous colorectal liver metastases: A systematic review and meta-analysis of completion rates and effects on survival

Background: Patients presenting with synchronous colorectal liver metastases are increasingly being considered for a curative treatment, and the liver-first approach is gaining popularity in this context. However, little is known about the completion rates of the liver-first approach and its effects on survival. Methods: A systematic review and meta-analysis of liver-first strategy for colorectal liver metastasis. The primary outcome was an assessment of the completion rates of the liver-first approach. Secondary outcomes included overall survival, causes of non-completion, and clinicopathologic data. Results: Seventeen articles were amenable for inclusion and the total study population was 1041. The median completion rate for the total population was 80% (range 20–100). The median overall survival for the completion and non-completion groups was 45 (range 12–69) months and 13 (range 10.5–25) months, respectively. Metadata showed a significant survival benefit for the completion group, with a univariate hazard ratio of 12.0 (95% confidence interval, range 5.7–24.4). The major cause of non-completion (76%) was liver disease progression before resection of the primary tumor. Pearson tests showed significant negative correlation between median number of lesions and median size of the largest metastasis and completion rate. Conclusions: The liver-first approach offers a complete resection to most patients enrolled, with an overall survival benefit when completion can be assured. One-fifth fails to return to intended oncologic therapy and the major cause is interim metastatic progression, most often in the liver. Risk of non-completion is related to a higher number of lesions and large metastases. The majority of studies stem from primary rectal cancers, which may influence on the return to intended oncologic therapy as well

Histopathological investigation of colon liver metastases–which factors affect survival after surgery?

Introduction: Novel therapeutic options have improved prognosis for patients with colonic liver metastases (CLM) over the last decades. Despite this, the challenge to select and stratify patients for optimal treatment regimen persists. This study aimed to evaluate established and novel histopathological features and investigate the impact on overall survival (OS) and recurrence in patients undergoing surgery for CLM. Methods: Two hundred and sixty patients who underwent resection of CLM with curative intent 2006–2017 were included in the study. Clinicopathological characteristics were retrieved from patient medical records. The following histopathological parameters were investigated: vascular/lymphatic invasion, perineural invasion, tumor regression grade (TRG), tumor growth pattern, pseudocapsule and acellular mucin. Histopathological traits were correlated to OS. Results: Vascular and lymphatic invasion, as well as perineural invasion, significantly correlated with an adverse prognosis hazard ratio (HR) = 1.7, 95% confidence interval (CI) 1.23–2.40 and HR = 1.7, 95% CI 1.20–2.51, respectively. Results retrieved from the study could not propose any novel explorative histopathological features (TRG, tumor growth pattern, pseudocapsule and acellular mucin) to be of significant value as comes correlation with patient OS. Discussion: Classical histopathological characteristics of previously reported influence on survival were confirmed, while more novel factors that has been proposed, like tumor growth pattern, tumor regression and grade and presence of a pseudocapsule, were not. Further studies are thus needed to identify better ways of understanding the impact of tumor microenvironment and tumor biology on patient outcome and not at least for stratification and improved treatment response

Intraductal papillary mucinous carcinoma versus pancreatic ductal adenocarcinoma : A systematic review and meta-analysis

Background: Previous studies have indicated that there may be a difference in tumor biology between intraductal papillary mucinous carcinoma (IPMC) and pancreatic ductal adenocarcinoma (PDAC). However, the data are still controversial. The aim of this systematic review and meta-analysis was to summarize and compare the outcome of IPMC and PDAC after surgical resection. Methods: Studies comparing IPMC and PDAC were identified using Medline and Embase search engines. Primary outcomes of interest were survival and recurrence. Secondary outcomes were clinicopathological characteristics. Meta-analysis of data was conducted using a random-effects model. Results: A total of 14 studies were included. Pooled analysis revealed an improved 5-year overall survival (OS) for IPMC compared to PDAC (OR 0.23, 95% CI 0.09–0.56). Both colloid and tubular IPMC showed improved 5-year OS compared to PDAC (OR 0.12, 95% CI 0.05–0.25 and OR 0.38, 95% CI 0.26–0.54, respectively). Median survival time ranged from 21 to 58 months in the IPMC group compared to 12–23 months in the PDAC group. No meta-analysis could be performed on recurrence or on time-to-event data. Descriptive data showed no survival difference for higher TNM stages. IPMC was more often found at a TNM-stage of 1 (OR 4.40, 95% CI 2.71–7.15) and had lower rates of lymph node spread (OR 0.43, 95% CI 0.32–0.57). Conclusion: Available data suggest that IPMC has a more indolent course with a better 5-year OS compared to PDAC. The histopathological features are less aggressive in IPMC. The reason may be earlier detection. However, for IPMC with higher TNM stages the survival seems to be similar to that of PDAC

Proteomic and genomic profiling of pancreatic cancer

Pancreatic cancer remains the most fatal human tumor type. The aggressive tumor biology coupled with the lack of early detection strategies and effective treatment are major reasons for the poor survival rate. Collaborative research efforts have been devoted to understand pancreatic cancer at the molecular level. Large-scale genomic studies have generated important insights into the genetic drivers of pancreatic cancer. In the post-genomic era, protein sequencing of tumor tissue, cell lines, pancreatic juice, and blood from patients with pancreatic cancer has provided a fundament for the development of new diagnostic and prognostic biomarkers. The integration of mass spectrometry and genomic sequencing strategies may help characterize protein identities and post-translational modifications that relate to a specific mutation. Consequently, proteomic and genomic techniques have become a compulsory requirement in modern medicine and health care. These types of proteogenomic studies may usher in a new era of precision diagnostics and treatment in patients with pancreatic cancer

Thymidylate synthase : A predictive biomarker in resected colorectal liver metastases receiving 5-FU treatment

Aim: To investigate the role of thymidylate synthase (TS) as a predictive biomarker in patients with resected colorectal liver metastases (CRLM). Materials & methods: PubMed, EMBASE and Cochrane Library were queried up to June 2017. Meta-analysis was performed using random-effects model. Risk of bias was assessed using funnel plots. Results: Six eligible studies were included, comprising a total of 542 patients. Meta-analysis demonstrated a trend to reduced overall survival in patients with resected CRLM with TS overexpression, with a hazard ratio of 1.13 (95% CI: 0.99-1.29; p = 0.08). In three studies where patients received systemic fluorouracil, the pooled hazard ratio was 2.25 (95% CI: 1.37-3.71; p = 0.001). Conclusion: TS appears to be a clinically relevant predictive biomarker in patients with resected CRLM receiving systemic 5-FU

Diagnosis and management of duodenal perforations: a narrative review

Duodenal perforation is a rare, but potentially life-threatening injury. Multiple etiologies are associated with duodenal perforations such as peptic ulcer disease, iatrogenic causes and trauma. Computed tomography with intravenous and oral contrast is the most valuable imaging technique to identify duodenal perforation. In some cases, surgical exploration may be necessary for diagnosis. Specific treatment depends upon the nature of the disease process that caused the perforation, the timing, location and extent of the injury and the clinical condition of the patient. Conservative management seems to be feasible in stable patients with sealed perforations. Immediate surgery is required for patients presenting with peritonitis and/or intra-abdominal sepsis. Minimally invasive techniques are safe and effective alternatives to conventional open surgery in selected patients with duodenal perforations. Here we review the current literature on duodenal perforations and discuss the outcomes of different treatment strategies

Changes in apparent diffusion coefficient and pathological response in colorectal liver metastases after preoperative chemotherapy

Background: The pathological response to preoperative chemotherapy of colorectal liver metastases (CRLMs) is predictive of long-term prognosis after liver resection. Accurate preoperative assessment of chemotherapy response could enable treatment optimization. Purpose: To investigate whether changes in lesion-apparent diffusion coefficient (ADC) measured with diffusion-weighted magnetic resonance imaging (MRI) can be used to assess pathological treatment response in patients with CRLMs undergoing preoperative chemotherapy. Material and Methods: Patients who underwent liver resection for CRLMs after preoperative chemotherapy between January 2011 and December 2019 were retrospectively included if they had undergone MRI before and after preoperative chemotherapy on the same 1.5-T MRI scanner with diffusion-weighted imaging with b-values 50, 400, and 800 s/mm2. The pathological chemotherapy response was assessed using the tumor regression grade (TRG) by AJCC/CAP. Lesions were divided into two groups: pathological responding (TRG 0–2) and non-responding (TRG 3). The change in lesion ADC after preoperative chemotherapy was compared between responding and non-responding lesions. Results: A total of 27 patients with 49 CRLMs were included, and 24/49 lesions showed a pathological chemotherapy response. After chemotherapy, ADC increased in both pathological responding (pretreatment ADC: 1.26 [95% confidence interval (CI)=1.06–1.37] vs. post-treatment ADC: 1.33 [95% CI=1.13–1.56] × 10−3 mm2/s; P = 0.026) and non-responding lesions (1.12 [95% CI=0.980–1.21] vs. 1.20 [95% CI=1.09–1.43] × 10−3 mm2/s; P = 0.018). There was no difference in median relative difference in ADC after chemotherapy between pathological responding and non-responding lesions (15.8 [95% CI=1.42–26.3] vs. 7.17 [95% CI=−4.31 to 31.2]%; P = 0.795). Conclusion: Changes in CRLM ADCs did not differ between pathological responding and non-responding lesions