MicroRNA-203 predicts human survival after resection of colorectal liver metastasis.

BackgroundResection of colorectal liver metastasis (CRLM) can be curative. Predicting which patients may benefit from resection, however, remains challenging. Some microRNAs (miRNAs) become deregulated in cancers and contribute to cancer progression. We hypothesized that miRNA expression can serve as a prognostic marker of survival after CRLM resection.ResultsMiR-203 was significantly overexpressed in tumors of short-term survivors compared to long-term survivors. R1/R2 margin status and high clinical risk score (CRS) were also significantly associated with short-term survival (both p = 0.001). After adjusting for these variables, higher miR-203 expression remained an independent predictor of shorter survival (p = 0.010). In the serum cohort, high CRS and KRAS mutation were significantly associated with short-term survival (p = 0.005 and p = 0.026, respectively). After adjusting for CRS and KRAS status, short-term survivors were found to have significantly higher miR-203 levels (p = 0.016 and p = 0.033, respectively).Materials and methodsWe employed next-generation sequencing of small-RNAs to profile miRNAs in solid tumors obtained from 38 patients who underwent hepatectomy for CRLM. To validate, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed on 91 tumor samples and 46 preoperative serum samples.ConclusionsAfter CRLM resection, short-term survivors exhibited significantly higher miR-203 levels relative to long-term survivors. MiR-203 may serve as a prognostic biomarker and its prognostic capacity warrants further investigation

Registry‐based randomized clinical trials in surgery: Working with ACS‐NSQIP and the AHPBA to conduct pragmatic trials

Randomized controlled trials (RCTs) represent the gold standard for evidence in clinical medicine because of their ability to account for the effects of unmeasured confounders and selection bias by indication. However, their complexity and immense costs limit their application, and thus the availability of high-quality data to guide clinical care. Registry-based RCTs are a type of pragmatic trial that leverages existing registries as a platform for data collection, providing a low-cost alternative for randomized studies. Herein, we describe the tenets of registry RCTs and the development of the first AHPBA/ACS-NSQIP-based registry trial

Cefoxitin versus piperacillin–tazobactam as surgical antibiotic prophylaxis in patients undergoing pancreatoduodenectomy: protocol for a randomised controlled trial

Introduction Although antibiotic prophylaxis is established in reducing postoperative surgical site infections (SSIs), the optimal antibiotic for prophylaxis in pancreatoduodenectomy (PD) remains unclear. The study objective is to evaluate if administration of piperacillin–tazobactam as antibiotic prophylaxis results in decreased 30-day SSI rate compared with cefoxitin in patients undergoing elective PD.Methods and analysis This study will be a multi-institution, double-arm, non-blinded randomised controlled superiority trial. Adults ≥18 years consented to undergo PD for all indications who present to institutions participating in the National Surgical Quality Improvement Program Hepato-Pancreato-Biliary (NSQIP HPB) Collaborative will be included. Data collection will use the NSQIP HPB Collaborative Surgical Clinical Reviewers. Patients will be randomised to either 1–2 g intravenous cefoxitin or 3.375–4.5 g intravenous piperacillin–tazobactam within 60 min of surgical incision. The primary outcome will be 30-day postoperative SSI rate following PD. Secondary outcomes will include 30-day postoperative mortality; specific postoperative complication rate; and unplanned reoperation, length of stay, and hospital readmission. A subset of patients will have bacterial isolates and sensitivities of intraoperative bile cultures and SSIs. Postoperative SSIs and secondary outcomes will be analysed using logistic regression models with the primary predictor as the randomised treatment group. Additional adjustment will be made for preoperative biliary stent presence. Additionally, bacterial cultures and isolates will be summarised by presence of bacterial species and antibiotic sensitivities.Ethics and dissemination This study is approved by the Institutional Review Board at Memorial Sloan Kettering Cancer Center. This trial will evaluate the effect of piperacillin–tazobactam compared with cefoxitin as antibiotic prophylaxis on the hazard of postoperative SSIs. The results will be disseminated regardless of the effect of the intervention on study outcomes. The manuscript describing the effect of the intervention will be submitted to a peer-reviewed journal when data collection and analyses are complete.Trial registration number NCT03269994

The role of laparoscopic staging in patients with incidental gallbladder cancer

AbstractBackgroundThe role of staging laparoscopy (SL) in patients with incidental gallbladder cancer (IGBC) is ill defined. This study evaluates the utility of SL with the aim of identifying variables associated with disseminated disease (DD).MethodsConsecutive patients with IGBC who underwent re-exploration between 1998 and 2009 were identified from a prospective database. The yield and accuracy of SL were calculated. Demographics, tumour- and treatment-related variables were correlated with findings of DD.ResultsOf the 136 patients submitted to re-exploration for possible definitive resection, 19 (14.0%) had DD. Staging laparoscopy was carried out in 46 (33.8%) patients, of whom 10 (21.8%) had DD (peritoneal disease [n= 6], liver metastases [n= 3], retroperitoneal disease [n= 1]). Disseminated disease was identified by SL in two patients (yield = 4.3%), whereas eight were diagnosed after conversion to laparotomy (accuracy = 20.0%). The likelihood of DD correlated closely with T-stage (T1b, n= 0; T2, n= 5 [7.0%], T3, n= 14 [26.0%]; P= 0.004). A positive margin at initial cholecystectomy (odds ratio [OR] 5.44, 95% confidence interval [CI] 1.51–24.37; P= 0.004) and tumour differentiation (OR 7.64, 95% CI 1.1–NA; P= 0.006) were independent predictors of DD on multivariate analysis.DiscussionDisseminated disease is relatively uncommon in patients with IGBC and SL provides a very low yield. However, patients with poorly differentiated, T3 or positive-margin gallbladder tumours are at high risk for DD and targeting these patients may increase the yield of SL

Impact of pre‐operative positron emission tomography in gallbladder cancer

BackgroundCurrent pre-operative staging methods for gallbladder cancer (GBC) are suboptimal in detecting metastatic disease. Positron emission tomography (PET) may have a role but data are lacking.MethodsPatients with GBC and PET assessed by a hepatobiliary surgeon in clinic between January 2001 and June 2013 were retrospectively reviewed. Computed tomography (CT)/magnetic resonace imaging (MRI) were correlated with PET scans and analysed for evidence of metastatic or locally unresectable disease. Medical records were reviewed to determine if PET scanning was helpful by preventing non-therapeutic surgery or enabling resection in patients initially deemed unresectable.ResultsThere were 100 patients including 63 incidental GBC. Thirty-eight patients did not proceed to surgery, 35 were resected and 27 patients were explored but had unresectable disease. PET was positive for metastatic disease in 39 patients (sensitivity 56%, specificity 94%). Five patients definitively benefitted from PET: in 3 patients PET found disease not seen on CT, and 2 patients with suspicious CT findings had negative PET and successful resections. In a further 12 patients PET confirmed equivocal CT findings. Three patients had additional invasive procedures performed owing to PET avidity in other sites. Utility of PET was higher in patients with suspicious nodal disease on CT [odds ratio (OR) 7.1 versus no nodal disease, P = 0.0004], and in patients without a prior cholecystectomy (OR 3.1 versus post-cholecystectomy, P = 0.04).ConclusionAddition of PET to conventional cross-sectional imaging has a modest impact on management pre-operatively particularly in patients without a prior cholecystectomy and to confirm suspicious nodal disease on CT

Changes in the management of benign liver tumours: an analysis of 285 patients

AbstractObjectivesBenign liver tumours (BLTs) are common and their management remains controversial. This study assesses the safety of a selective management approach.MethodsPatients with BLT were identified from an institutional database. Patients with simple cysts or an incidental BLT in the setting of metastasis or concomitant malignancy were excluded.ResultsA total of 285 patients presenting during the period from January 1992 to December 2009 with haemangioma (53.0%), focal nodular hyperplasia (23.9%), adenoma (10.2%) or indeterminate/other lesions (13.0%) were evaluated. Of these, 117 patients (41.1%) underwent immediate resection and 168 patients (58.9%) were followed with serial imaging (median follow‐up: 30 months). During observation, eight patients (4.8%) underwent resection for tumour growth, inability to exclude malignancy or symptoms; no patients demonstrated malignant transformation or tumour‐related complications. During the study period, the number of BLTs evaluated and the proportion of patients observed increased from 129 BLTs of which 36.4% were observed in 1992–2002 to 156 BLTs of which 71.2% were observed in 2003–2009 (P < 0.001). Diagnostic uncertainty led to resection in 29.5% of patients during the earlier period, but in only 13.4% during the more recent 7 years (P < 0.05).ConclusionsAsymptomatic BLTs without concern for malignancy or adenoma can be safely observed with minimal risk for misdiagnosis. Patients selected for observation rarely require resection or develop tumour‐related complications

Impact of pre‐operative positron emission tomography in gallbladder cancer

BackgroundCurrent pre-operative staging methods for gallbladder cancer (GBC) are suboptimal in detecting metastatic disease. Positron emission tomography (PET) may have a role but data are lacking.MethodsPatients with GBC and PET assessed by a hepatobiliary surgeon in clinic between January 2001 and June 2013 were retrospectively reviewed. Computed tomography (CT)/magnetic resonace imaging (MRI) were correlated with PET scans and analysed for evidence of metastatic or locally unresectable disease. Medical records were reviewed to determine if PET scanning was helpful by preventing non-therapeutic surgery or enabling resection in patients initially deemed unresectable.ResultsThere were 100 patients including 63 incidental GBC. Thirty-eight patients did not proceed to surgery, 35 were resected and 27 patients were explored but had unresectable disease. PET was positive for metastatic disease in 39 patients (sensitivity 56%, specificity 94%). Five patients definitively benefitted from PET: in 3 patients PET found disease not seen on CT, and 2 patients with suspicious CT findings had negative PET and successful resections. In a further 12 patients PET confirmed equivocal CT findings. Three patients had additional invasive procedures performed owing to PET avidity in other sites. Utility of PET was higher in patients with suspicious nodal disease on CT [odds ratio (OR) 7.1 versus no nodal disease, P = 0.0004], and in patients without a prior cholecystectomy (OR 3.1 versus post-cholecystectomy, P = 0.04).ConclusionAddition of PET to conventional cross-sectional imaging has a modest impact on management pre-operatively particularly in patients without a prior cholecystectomy and to confirm suspicious nodal disease on CT

Pharmacologic Prophylaxis, Postoperative INR, and Risk of Venous Thromboembolism after Hepatectomy

Pharmacologic prophylaxis (PP) is recommended for patients undergoing general surgical procedures with at least moderate risk of venous thromboembolism (VTE). The role of PP in patients undergoing hepatectomy is controversial, however, due to concerns regarding postoperative liver dysfunction and bleeding. We conducted a retrospective analysis of a prospectively maintained institutional database in order to clarify the relationship between PP, postoperative INR, and risk of VTE. Postoperative VTE occurred in 55 of 2,147 patients (2.6 %) and was independently associated with advanced age, higher BMI, longer procedure time, and development of a major complication, as well as higher postoperative INR (a parts per thousand yen1.5 versus < 1.5: OR 2.50, P = 0.006). Patients undergoing more extensive liver resection with higher postoperative INR were less likely to receive PP, but receipt of PP demonstrated no relationship with either VTE incidence or hemorrhagic complications. In this large single-institution study, incidence of VTE was not associated with PP but was associated with higher postoperative INR, contrary to the notion that postoperative liver dysfunction is protective against VTE. The interplay between prothrombotic and antithrombotic mechanisms in posthepatectomy patients must be more completely characterized before broad recommendations can be made regarding PP use in these patients