Diagnostic accuracy of staging laparoscopy for detecting metastasized or locally advanced perihilar cholangiocarcinoma: a systematic review and meta-analysis.
ABSTRACT: Despite extensive preoperative staging, still almost half of patients with potentially resectable perihilar cholangiocarcinoma (PHC) have locally advanced or metastasized disease upon exploratory laparotomy. The value of routine staging laparoscopy (SL) in these patients remains unclear with varying results reported in the literature. The aim of the present systematic review was to provide an overview of studies on SL in PHC and to define its current role in preoperative staging.A systematic review and meta-analysis were performed in PubMed and EMBASE regarding studies providing data on the diagnostic accuracy of SL in PHC. Primary outcome measures were the overall yield and sensitivity to detect unresectable disease. Secondary outcomes were the yield and sensitivity for recent studies (after 2010) and large study cohorts (?100 patients) and specific (metastatic) lesions. Methodological quality of studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool.From 173 records, 12 studies including 832 patients met the inclusion criteria. The yield of SL in PHC varied from 6.4 to 45.0 % with a pooled yield of 24.4 % [95 % confidence interval (CI) 16.4-33.4]. Sensitivity to detect unresectable disease ranged from 31.6 to 75 % with a pooled sensitivity of 52.2 % (95 % CI 47.1-57.2). Sensitivity was highest for peritoneal metastases (80.7 %, 95 % CI 70.9-88.3). Subgroup analysis revealed that the yield and sensitivity tended to be lower for studies after 2010. Considerable heterogeneity was detected among the studies.The results of the pooled analyses suggest that one in four patients with potentially resectable PHC benefits from SL. Given considerable heterogeneity, a trend to lower yield in more recent studies and further improvement of preoperative imaging over time, the routine use of SL seems discouraging. Studies that identify predictors of unresectability, that enable selection of patients who will benefit the most from this procedure, are needed.
Project description:Nearly half of patients with perihilar cholangiocarcinoma (PHC) have incurable tumors at laparotomy. Staging laparoscopy (SL) potentially detects metastases or locally advanced disease, thereby avoiding unnecessary laparotomy. However, the diagnostic yield of SL has decreased with improved imaging in recent years.The aim of this study was to identify predictors for detecting metastasized or locally advanced PHC at SL and to develop a risk score to select patients who may benefit most from this procedure.Data of patients with potentially resectable PHC who underwent SL between 2000 and 2015 in our center were retrospectively analyzed. Multivariable logistic regression analysis was used to identify independent predictors and to develop a preoperative risk score.Unresectable PHC was detected in 41 of 273 patients undergoing SL (yield 15 %). Overall sensitivity of SL was 30 %, with highest sensitivity for detecting peritoneal metastases (73 %). Preoperative imaging factors that were independently associated with unresectability at SL were tumor size ?4.5 cm, bilateral portal vein involvement, suspected lymph node metastases, and suspected (extra)hepatic metastases on imaging without the possibility of diagnosis by percutaneous- or endoscopic ultrasound-guided biopsy. The derived preoperative risk score showed good discrimination to predict unresectability (area under the curve 0.77, 95 % confidence interval 0.68-0.86) and identified three subgroups with a predicted low-risk of 7 % (N = 203 patients), intermediate-risk of 21 % (N = 39), and high-risk of 58 % (N = 31).A selective approach for SL in PHC is recommended since the overall yield is low. The proposed preoperative risk score is useful in selecting patients for SL.
Project description:Preoperative biliary drainage is often initiated with endoscopic retrograde cholangiopancreatography (ERCP) in patients with potentially resectable perihilar cholangiocarcinoma (PHC), but additional percutaneous transhepatic catheter (PTC) drainage is frequently required. This study aimed to develop and validate a prediction model to identify patients with a high risk of inadequate ERCP drainage.Patients with potentially resectable PHC and (attempted) preoperative ERCP drainage were included from two specialty center cohorts between 2001 and 2013. Indications for additional PTC drainage were failure to place an endoscopic stent, failure to relieve jaundice, cholangitis, or insufficient drainage of the future liver remnant. A prediction model was derived from the European cohort and externally validated in the USA cohort.Of the 288 patients, 108 (38%) required additional preoperative PTC drainage after inadequate ERCP drainage. Independent risk factors for additional PTC drainage were proximal biliary obstruction on preoperative imaging (Bismuth 3 or 4) and predrainage total bilirubin level. The prediction model identified three subgroups: patients with low risk (7%), moderate risk (40%), and high risk (62%). The high-risk group consisted of patients with a total bilirubin level above 150 µmol/L and Bismuth 3a or 4 tumors, who typically require preoperative drainage of the angulated left bile ducts. The prediction model had good discrimination (area under the curve 0.74) and adequate calibration in the external validation cohort.Selected patients with potentially resectable PHC have a high risk (62%) of inadequate preoperative ERCP drainage requiring additional PTC drainage. These patients might do better with initial PTC drainage instead of ERCP.
Project description:Patients presenting with synchronous or metachronous colorectal cancer liver metastases (CLM) should be evaluated for multimodal management with curative intent. Preoperative systemic chemotherapy shows beneficial impact on adjuvant progression-free survival and also borderline on overall survival, without significantly increasing initially R0 resectable patients postoperative complication rates. Postoperative chemotherapy recommended based on the perioperative trial experience for those patients achieving at least stable disease during preoperative chemotherapy, or based on the adjuvant trials for patients receiving upfront resection. 'Borderline' resectable CLM, preoperative chemotherapy plays an important role in both in achievement of a resectable status and improvement of prognosis. Recent 4 drug combinations demonstrated response rates up to 80% even for advanced disease and are thus promising regimens for further evaluation in patients with resectable or unresectable liver-limited (+/- lung) disease.
Project description:OBJECTIVE:Although the prognostic significance of systematic inflammation-based scores, such as the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the prognostic nutritional index (PNI), has been explored in pancreatic cancers, few reports have investigated the lymphocyte-to-monocyte ratio (LMR). We aimed to retrospectively investigate the prognostic value of the preoperative LMR in patients with resectable pancreatic head cancer (PHC). METHODS:From 2005 to 2016, 165 patients underwent pancreatoduodenectomy for PHC. All samples of peripheral blood were collected within 2 weeks prior to surgery. The best cutoff values of the LMR for predicting survival were determined by using a minimum p value approach (cut-off value: 2.8). The clinicopathological features of LMR <2.8 (n = 25) and ?2.8 (n = 140) were compared. RESULTS:Patients with LMR ?2.8 showed significantly lower NLR and PLR, and significantly higher PNI. Levels of CEA and CA19-9 were similar, and the pathological findings were comparable between the groups. The overall survival of patients with LMR ?2.8 (66.2% at 1 year) was superior to that of patients with LMR <2.8 (36.1% at 1 year, p = 0.015). Multivariate analysis identified LMR <2.8 (hazard ratio 1.72, 95% CI 1.02-2.89, p = 0.042), lymphatic and venous invasion and positive surgical margin as independent prognostic factors. CONCLUSIONS:LMR may carry important prognostic information for patients with resectable PHC. Preoperative LMR may be considered for use in risk stratification for individual patients with PHC.
Project description:Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with postoperative mortality ranging from 5% to 18%. The aim of this study was to develop a preoperative risk score for postoperative mortality after liver resection for PHC, and to assess the effect of biliary drainage of the future liver remnant (FLR).A consecutive series of 287 patients submitted to major liver resection for presumed PHC between 1997 and 2014 at 2 Western centers was analyzed; 228 patients (79%) underwent preoperative drainage for jaundice. Future liver remnant volumes were calculated with CT volumetry and completeness of FLR drainage was assessed on imaging. Logistic regression was used to develop a mortality risk score.Postoperative mortality at 90 days was 14% and was independently predicted by age (odds ratio [OR] per 10 years = 2.1), preoperative cholangitis (OR = 4.1), FLR volume <30% (OR = 2.9), portal vein reconstruction (OR = 2.3), and incomplete FLR drainage in patients with FLR volume <50% (OR = 2.8). The risk score showed good discrimination (area under the curve = 0.75 after bootstrap validation) and ranking patients in tertiles identified 3 (ie low, intermediate, and high) risk subgroups with predicted mortalities of 2%, 11%, and 37%. No postoperative mortality was observed in 33 undrained patients with FLR volumes >50%, including 10 jaundiced patients (median bilirubin level 11 mg/dL).The mortality risk score for patients with resectable PHC can be used for patient counseling and identification of modifiable risk factors, which include FLR volume, FLR drainage status, and preoperative cholangitis. We found no evidence to support preoperative biliary drainage in patients with an FLR volume >50%.
Project description:Background:Currently, preoperative chemoradiotherapy, perioperative chemotherapy and preoperative chemotherapy are recommended by NCCN, ESMO and Japanese guidelines respectively for resectable esophageal and junctional cancer. However, these recommendations are mainly based on esophageal cancer research. Therefore, specific for esophagogastric junction cancer, we conducted the first systematic review and network meta-analysis to rank all potential treatments simultaneously and hierarchically. Methods:Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO and ESMO Meeting Library from inception to September 2018. Regarding time-to-event survival data, randomized controlled trials featuring comparisons between different multimodal treatments against resectable esophagogastric junction cancer were eligible. Overall survival was the endpoint. Network calculation was based on a random-effects model and the relative ranking of each node was numerically indicated by P-score (CRD42018110369, registration identifier of the meta-analysis in PROSPERO.). Results:Eight studies were included in our systematic review, corresponding to 1218 patients. Regarding overall survival, 'PreCRT' (preoperative chemoradiotherapy) topped the hierarchy (HR 1.00, P-score = 0.823), better than 'PeriCT' (perioperative chemotherapy; HR 1.32, P-score = 0.591) and 'PreCT' (preoperative chemotherapy; HR 1.54, P-score = 0.428). In sensitivity analyses, irrespective of interchanging to fixed-effects model or removing potentially heterogeneous studies, relative rankings remained stable and 'PreCRT' was still the optimal node. Conclusion:Preoperative chemoradiotherapy could potentially be the optimal multimodal treatment, which displayed more overall survival benefits than perioperative chemotherapy and preoperative chemotherapy among resectable esophagogastric junction cancer patients. To further verify our pooled results, more randomized trials will be needed to compare preoperative chemoradiotherapy with perioperative chemotherapy (especially FLOT-based regimens).
Project description:BACKGROUND:Postoperative radiation therapy for soft tissue sarcomas demonstrated good local recurrence-free survival rates and survival outcomes. However, the results remained controversial. This study aimed to evaluate the role of preoperative and postoperative radiation therapy for the treatment of resectable soft tissue sarcomas. METHODS:The electronic database PubMed, MEDLINE, Cochrane Library, and EMBASE were performed from inception till 30 November, 2019. The effect of preoperative versus postoperative radiation therapy on resectable soft tissue sarcomas was compared and then assessed. RESULTS:A total of 15 studies with 12,813 patients were included, and most of these had acceptable quality scores. Of these, 10 studies reported data on local recurrence. The pooled results indicated no significant differences between preoperative radiotherapy and postoperative radiotherapy groups for local recurrence, with a risk ratio (RR) and 95% confidence interval (CI) of 0.84 (95%CI?=?0.58-1.21). No difference was observed in the overall survival and distant metastasis between the two groups. According to the pooled results, preoperative radiotherapy group showed a significant risk for complications (RR?=?2.11, 95%CI?=?1.36-3.27). CONCLUSIONS:The postoperative radiation therapy does not increase the local recurrence, overall survival, and distant metastasis, but might result in lowering complications.
Project description:BACKGROUND AND STUDY AIMS:It is unclear to what extent EUS influences the surgical management of patients with pancreatic adenocarcinoma. This systematic review sought to determine if EUS evaluation improves the identification of unresectable disease among adults with pancreatic adenocarcinoma. PATIENTS AND METHODS:We searched MEDLINE, EMBASE, bibliographies of included articles and conference proceedings for studies reporting original data regarding surgical management and/or survival among patients with pancreatic adenocarcinoma, from inception to January 7th 2017. Our main outcome was the incremental benefit of EUS for the identification of unresectable disease (IBEUS). The pooled IBEUS were calculated using random effects models. Heterogeneity was explored using stratified meta-analysis and meta-regression. RESULTS:Among 4,903 citations identified, we included 8 cohort studies (study periods from 1992 to 2007) that examined the identification of unresectable disease (n = 795). Random effects meta-analysis suggested that EUS alone identified unresectable disease in 19% of patients (95% confidence interval [CI], 10-33%). Among those studies that considered portal or mesenteric vein invasion as potentially resectable, EUS alone was able to identify unresectable disease in 14% of patients (95% CI 8-24%) after a CT scan was performed. LIMITATIONS:The majority of the included studies were retrospective. CONCLUSIONS:EUS evaluation is associated with increased identification of unresectable disease among adults with pancreatic adenocarcinoma.
Project description:The purpose of this study was to evaluate preoperative treatment with full-dose gemcitabine, oxaliplatin, and radiation therapy (RT) in patients with localized pancreatic cancer.Eligibility included confirmation of adenocarcinoma, resectable or borderline resectable disease, a performance status ≤2, and adequate organ function. Treatment consisted of two 28-day cycles of gemcitabine (1 g/m(2) over 30 minutes on days 1, 8, and 15) and oxaliplatin (85 mg/m(2) on days 1 and 15) with RT during cycle 1 (30 Gray [Gy] in 2-Gy fractions). Patients were evaluated for surgery after cycle 2. Patients who underwent resection received 2 cycles of adjuvant chemotherapy.Sixty-eight evaluable patients received treatment at 4 centers. By central radiology review, 23 patients had resectable disease, 39 patients had borderline resectable disease, and 6 patients had unresectable disease. Sixty-six patients (97%) completed cycle 1 with RT, and 61 patients (90%) completed cycle 2. Grade ≥3 adverse events during preoperative therapy included neutropenia (32%), thrombocytopenia (25%), and biliary obstruction/cholangitis (14%). Forty-three patients underwent resection (63%), and complete (R0) resection was achieved in 36 of those 43 patients (84%). The median overall survival was 18.2 months (95% confidence interval, 13-26.9 months) for all patients, 27.1 months (95% confidence interval, 21.2-47.1 months) for those who underwent resection, and 10.9 months (95% confidence interval, 6.1-12.6 months) for those who did not undergo resection. A decrease in CA 19-9 level after neoadjuvant therapy was associated with R0 resection (P = .02), which resulted in a median survival of 34.6 months (95% confidence interval, 20.3-47.1 months). Fourteen patients (21%) are alive and disease free at a median follow-up of 31.4 months (range, 24-47.6 months).Preoperative therapy with full-dose gemcitabine, oxaliplatin, and RT was feasible and resulted in a high percentage of R0 resections. The current results are particularly encouraging, because the majority of patients had borderline resectable disease.
Project description:Neoadjuvant treatment has proven beneficial for many gastrointestinal (GI) malignancies, but no phase III trials have been completed examining this approach in pancreatic cancer. This meta-analysis examines the best available phase II trials using neoadjuvant treatment for resectable and borderline/unresectable pancreatic adenocarcinoma.Phase II trials were identified using a MEDLINE search, and the Cochrane Central Register of Controlled Trials from 1960 to July 2010. Patients were divided into 2 groups: Patients with initially resectable tumors (group A), and patients with borderline/unresectable tumors (group B). Primary outcome measures were rate of resection and survival. Pooled proportions and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies.A total of 14 phase II clinical trials including 536 patients were analyzed. After treatment, resectability was 65.8% (95% CI, 55.4-75.6%) compared with 31.6% in group B (95% CI, 14.0-52.5%). A partial response was observed in patients with borderline/unresectable tumors; 31.8 (95% CI, 24.2-39.8%) in group B and 9.5% (95% CI, 2.9-19.4%) in group A (P = .003). Progressive disease was seen in 17.0% (95% CI, 11.9-22.7) of patients in group A versus 21.8% (95% CI, 10.1-36.5%) in group B (P = .006). Median survival in resected patients was 23 months for group A and 22 months for group B.Neoadjuvant treatment seems to have some activity in patients with borderline/unresectable pancreatic adenocarcinoma. Nearly one third of tumors initially deemed marginal for operative intervention were able to be ultimately resected after treatment. Until more effective targeted chemotherapeutics are developed, the only group of patients with pancreatic cancer that may benefit from neoadjuvant treatment are those with locally advanced disease.