The impact of tranexamic acid on administration of red blood cell transfusions for resection of colorectal liver metastases.

BACKGROUND: Red blood cell transfusions (RBCT) remain a concern for patients undergoing hepatectomy. The effect of tranexamic acid (TXA), an anti-fibrinolytic, on receipt of RBCT in colorectal liver metastases (CRLM) resection was examined. METHODS: Hepatectomies for CRLM over 2009-2014 were included. Primary outcome was 30-day receipt of RBCT. Secondary outcomes were 30-day major morbidity (Clavien-Dindo III-V) and 90-day mortality. Multivariable modelling examined the adjusted association between TXA and outcomes. RESULTS: Of 433 included patients, 146 (34%) received TXA. TXA patients were more likely to have inflow occlusion (41.8% vs. 23.1%; p < 0.01) and major hepatectomies (56.1% vs. 45.6%; p = 0.0193). TXA was independently associated with lower risk of RBCT (Relative risk (RR) 0.59; 95% confidence interval (95%CI): 0.42-0.85), but not with 30-day major morbidity (adjusted RR 1.02; 95%CI: 0.64-1.60) and 90-day mortality (univariable RR 0.99; 95%CI: 0.95-1.03). CONCLUSION: Intraoperative TXA was associated with a 41% reduction in risk of 30 -day receipt of RBCT after hepatectomy for CRLM. This finding is important to potentially improve healthcare resource allocation and patient outcomes. Pending further evidence, intraoperative TXA may be an effective method of reducing RBCT in hepatectomy for CRLM.

Elevated Lactate is Independently Associated with Adverse Outcomes Following Hepatectomy.

BACKGROUND: Arterial lactate is frequently monitored to indicate tissue hypoxia and direct therapy. We sought to determine whether early post-hepatectomy lactate (PHL) is associated with adverse outcomes and define factors associated with PHL. METHODS: Hepatectomy patients at a single institution from 2003 to 2012 with PHL available were included. Univariable and multivariable analyses examined factors associated with PHL and the relationship between PHL and 30-day major morbidity (Clavien grade III-V), 90-day mortality, and length of stay (LOS). RESULTS: Of 749 hepatectomies, 490 were included of whom 71.4% had elevated PHL (≥2 mmol/L). Cirrhosis (coefficient 0.31, p = 0.039), Charlson comorbidity index (coefficient 0.05, p < 0.001), major resections (coefficient 0.34, p < 0.001), procedure time (coefficient 0.08, p < 0.001), and blood loss (coefficient 0.11, p < 0.001) were associated with PHL. As lactate increased from <2 to ≥6 mmol/L, morbidity rose from 11.6 to 40.6%, and mortality from 0.7 to 22.7%. PHL was independently associated with 90-day mortality (OR 1.52 p < 0.001) and 30-day morbidity (OR 1.19, p = 0.002), but not LOS (rate ratio 1.03, p = 0.071). CONCLUSION: Patients with elevated PHL in the initial postoperative period should be carefully monitored due to increased risk of major morbidity and mortality. Further research on the impact of lactate-directed fluid therapy is warranted.

Is central venous pressure still relevant in the contemporary era of liver resection?

BACKGROUND: Perioperative red blood cell transfusion (RBCT) remains common after liver resection and carries risk of increased morbidity and worse oncologic outcomes. We sought to assess the factors associated with perioperative RBCT after hepatectomy with a focus on intraoperative hemodynamics. METHODS: We performed a retrospective review of our prospective hepatectomy database, supplemented by a review of anesthetic records of all patients undergoing hepatectomy with hemodynamic monitoring (arterial and central venous pressures [CVP]) from 2003-2012. Primary outcome was perioperative RBCT (during and within 30 d after surgery). After descriptive and univariate comparisons, multivariate analysis was conducted to identify factors associated with RBCT. RESULTS: Of 851 hepatectomies, 530 had complete hemodynamic data and 30.2% (161 of 530) received RBCT. Among transfused patients, female gender (P = 0.01), preoperative anemia (P < 0.001), and major liver resection (P = 0.02) were more common. Mean estimated blood loss was 1.1 L higher (2.0 versus 0.9 L; P < 0.001) and operating time was 1.1 h longer (5.8 versus 4.7 h; P < 0.001) in transfused patients. Trends in intraoperative CVP differed significantly based on transfusion status (P = 0.007). Independent factors associated with RBCT included female gender (odds ratio [OR], 2.27; P = 0.01), preoperative anemia (OR, 2.38; P = 0.03), longer operative time (OR, 1.19 per hour; P = 0.03), and higher intraoperative CVP at 1 h during surgery (OR, 1.10 per mm Hg; P = 0.005). CONCLUSIONS: Likelihood of RBCT is independently associated with female gender, preoperative anemia, longer operative time, and higher intraoperative CVP. Focus on management of preoperative anemia, operative efficiency, and low intraoperative CVP is needed to minimize the need for RBCTs.

The Impact of Perioperative Red Blood Cell Transfusions on Long-Term Outcomes after Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: Red blood cell transfusions (RBCTs) are associated with cancer recurrence following resection of colorectal cancer. Their impact after colorectal liver metastases (CRLM) resection remains debated. We sought to explore the association between perioperative RBCT and oncologic outcomes following resection of CRLM. METHODS: We reviewed patients undergoing partial hepatectomy for CRLM from 2003 to 2012 at a single institution. Date of death was abstracted from a validated population-based cancer registry. Primary outcome was overall survival (OS). Secondary outcome was recurrence-free survival (RFS). Survivals were estimated using Kaplan-Meier methods and compared with log-rank test based on transfusion status. Cox regression analysis examined the association of RBCT with OS and RFS, while adjusting for age, preoperative chemotherapy, Clinical Risk Score, and period of treatment (2003-2007 vs. 2008-2012). RESULTS: Among 483 patients, 27.5 % received RBCT. Ninety-day postoperative mortality was 4.8 %. At median follow-up of 33 (interquartile range 20.1-54.8) months, 5-year OS was inferior in transfused patients (45.9 vs. 61.0 %; p < 0.0001). Five-year RFS was decreased with RBCT (15.5 vs. 31.6 %; p < 0.0001). The difference persisted when considering only 90-day survivors for 5-year OS (53.1 vs. 61.9 %, p = 0.023) and RFS (15.6 vs. 31.6 %; p < 0.0001). After adjustment for prognostic factors, RBCT was independently associated with decreased OS (hazard ratio 2.24; 95 % confidence interval 1.60-3.15) and RFS (hazard ratio 1.71; 95 % confidence interval 1.28-2.28). CONCLUSIONS: Perioperative RBCT is independently associated with decreased OS and RFS following hepatectomy for CRLM. Interventions to minimize and rationalize the use of RBCT for hepatectomy are warranted to mitigate this detrimental effect on long-term outcomes.

The impact of portal pedicle clamping on survival from colorectal liver metastases in the contemporary era of liver resection: a matched cohort study.

INTRODUCTION: Portal pedicle clamping (PPC) may impact micro-metastases' growth. This study examined the association between PPC and survival after a hepatectomy for colorectal liver metastases (CRLM). METHODS: A matched cohort study was conducted on hepatectomies for CRLM at a single institution (2003-2012). Cohorts were selected based on PPC use, with 1:1 matching for age, time period and the Clinical Risk Score. Outcomes were overall and recurrence-free survival (OS and RFS). Cox regression was performed to assess the association between PPC and survival. RESULTS: Of 481 hepatectomies, 26.9% used PPC. One hundred and ten pairs of patients were matched in the cohorts. There was no significant difference in OS [hazard ratio (HR) 1.18; 95% confidence interval (CI): 0.76-1.83], with a 5-year OS of 57.8% (95%CI: 52.4-63.2%) with PPC versus 62.3% (95%CI: 57.1-67.5%) without. Five-year RFS did not differ (HR 0.98; 95%CI: 0.71-1.35) with 29.7% (95%CI: 24.9-34.5%) with PPC versus 28.0% (95%CI: 23.2-32.8%) without. When adjusting for extent of resection, transfusion, operative time and surgeon, there was no difference in OS (HR 0.91; 95%CI: 0.52-1.60) or RFS (HR: 0.86; 95%CI: 0.57-1.30). CONCLUSIONS: PPC was not associated with a significant difference in OS or RFS in a hepatectomy for CRLM. PPC remains a safe technique during hepatectomy.

Utility of preoperative imaging in evaluating colorectal liver metastases declines over time.

OBJECTIVES: Reports on the sensitivity and accuracy of contrast-enhanced helical computed tomography (HCT) in the preoperative evaluation of colorectal liver metastases (CLM) have been conflicting. Few studies have controlled for and reported on the time interval between HCT and eventual surgery. METHODS: A multi-institution, retrospective review of consecutive patients who underwent hepatic resection for CLM from January 1999 to September 2004 was conducted. Data regarding lesion characteristics and resectability were extracted from radiology reports, operative findings and histopathological records. Findings in HCT were evaluated according to their sensitivity for detecting CLM and ability to predict resectability. RESULTS: A total of 217 consecutive patients who underwent hepatic resection for CLM were identified. The overall sensitivity of HCT for detection of CLM was 83.2%. Prolonged time between imaging and surgery was a negative predictor for HCT sensitivity in univariate and multivariate analysis (P < 0.001). In predicting resectability, preoperative HCT was accurate 77.0% of the time. The time interval to surgery was negatively correlated with HCT prediction accuracy in univariate and multivariate analyses (P < 0.001). CONCLUSIONS: The utility of HCT as a preoperative tool to evaluate CLM is inversely proportional to the time interval between imaging and surgery. This may explain conflicting reports of the accuracy of HCT in the current literature.

The impact of red blood cell transfusions on perioperative outcomes in the contemporary era of liver resection.

BACKGROUND: Perioperative red blood cell transfusions (RBCTs) are common in patients undergoing partial hepatectomy. We sought to explore the relationship between RBCTs and posthepatectomy perioperative outcomes in the contemporary surgical era. METHODS: We reviewed all patients undergoing partial hepatectomy from 2003 to 2012. Primary outcome was 30-day major morbidity (MM). We compared patients who did and received perioperative RBCT (defined as from time of operation until 30 days postoperatively. Multivariate analysis was performed to identify factors associated with MM and duration of stay, using logistic and negative binomial regression. RESULTS: Among 712 patients, 16.8% experienced MM, of whom 53.3% received RBCT. Patients who received RBCT experienced MM more commonly (30.8% vs 11.1%; P < .001). On multivariate analysis, the only factors associated with MM were age (relative risk [RR], 1.03; 95% CI, 1.00-1.06), greater operative time (RR, 1.29; 95% CI, 1.11-1.50), and RBCT (RR, 3.57; 95% CI, 1.81-7.04). RBCT was associated independently with a greater duration of stay (RR, 1.47; 95% CI, 1.13-1.91). CONCLUSION: Receipt of RBCT is associated independently with perioperative MM and prolonged hospitalization after partial hepatectomy. These findings further the rationale supporting the need for a strategy of blood management to decrease the use of RBCT after hepatectomy.

The Effect of Early Postoperative Non-Steroidal Anti-Inflammatory Drugs on Pancreatic Fistula Following Pancreaticoduodenectomy.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are used commonly for postoperative analgesia but can potentially impair healing. Their effect on pancreaticoduodenectomy (PD) outcomes is unknown. We sought to examine the impact of early postoperative NSAIDs on pancreatic fistula (PF) after PD. METHODS: We reviewed our prospective pancreatectomy database supplemented by medication administration records, including all PDs from 2002 to 2012. Primary outcome was occurrence of clinically significant (grade B-C) PF. Secondary outcomes included major morbidity (Clavien grade III-V) and 90-day mortality. Patients were compared based on early postoperative NSAID use (first 3 days following surgery) using univariate and multivariate analyses. Subgroup analyses were conducted based on NSAID type (COX-2 inhibitors and non-selective inhibitors). RESULTS: We included 251 PDs, of whom 127 (50.6%) patients received NSAIDs postoperatively (35.5% COX-2 inhibitors, 18.3% non-selective inhibitors, and 4.4% both). Use of any NSAIDs was associated with a non-significant increase in PF (16.5 vs 11.3%%; p = 0.23), and no difference in major morbidity and mortality. Use of non-selective inhibitors was not associated with an increase in PF (8.7 vs 15.1%; p = 0.256). COX-2 inhibitors were associated with increased PF (20.2 vs 10.5 %; p = 0.033), but no difference in major morbidity or mortality. After adjusting for Charlson comorbidity and estimated blood loss, use of COX-2 inhibitors was independently associated with PF (odds ratio 2.12; p = 0.044). CONCLUSIONS: COX-2 inhibitors are associated with PF in the early postoperative period. While non-selective inhibitors appear safe in this setting, caution is warranted with the use of COX-2 inhibitors.

Minimising blood loss and transfusion requirements in hepatic resection.

BACKGROUND: Substantial blood loss and the requirement for blood transfusion remain major considerations for hepatic surgeons. We analysed the impact of a systematic protocol aimed at reducing intraoperative blood loss and homologous blood (HB) transfusion associated with hepatic resection. METHODS: Prospective clinical data were collected from 151 elective liver resections performed during the period between 1980 and 1999. Further data directly related to blood loss and anaesthesia were retrospectively collected from the anaesthetic intra-operative record. Strategies implemented in 1991 included preoperative autologous blood donation, low central venous pressure anaesthesia, aprotinin administration, ultrasonic dissection, hepatic vascular inflow occlusion and a Cell Saver. Blood loss and transfusion requirements were studied before and after the implementation of these strategies. RESULTS: There was no difference in the patient demographics, indications for operation or the scope of resections in the two time periods evaluated. Blood-saving strategies resulted in decreased estimated blood loss (4500 mL vs. 1000 mL p<0.001). In addition, the number of patients requiring transfusion decreased (91.8% vs. 25.5% respectively, p<0.001) and the mean number of units of HB transfusion was lower (I 3.7 vs. 2.3, p<0.001). Morbidity and mortality were also decreased (57.1% vs. 25.5%, p<0.001 and 10.2% and 4.9% p<0.001, respectively). No complications directly referrable to low CVP anesthesia were identified. CONCLUSION: Systematic implementation of strategies designed to control blood loss are effective and may reduce morbidity and mortality associated with hepatic resections.

Impact of lymph node retrieval and pathological ultra-staging on the prognosis of stage II colon cancer.

BACKGROUND AND OBJECTIVES: A minimum number of lymph nodes must be assessed for accurate diagnosis of stage II colon cancer. We assessed number of lymph nodes retrieved, pathological ultra-staging, and outcome in stage II colon cancer. MATERIALS AND METHODS: Consecutively treated patients with stage II colon cancer were identified. Baseline and outcome data were collected. Retrospective ultra-staging using lymphovascular invasion (LVI) and nodal micrometastases was performed. Patients were divided into two groups: group I had 6 nodes retrieved. Survival was analyzed. RESULTS: One hundred and fifteen patients were included in the study. The 5 year overall survival was worse in group I versus II (P = 0.03). LVI and micrometastases were identified but neither predicted survival. Disease failure in group I was due to distant metastases rather than local recurrence. CONCLUSIONS: Inadequate retrieval and assessment of lymph nodes is associated with worse outcome in stage II colon cancer patients. Recurrence patterns support the hypothesis that disease recurrence occurred due to inaccurate staging. In this small study, LVI or nodal micrometastases did not predict survival. Maximal attention should be paid to the total number of lymph nodes retrieved before embarking on potentially more resource intensive staging methods.

Pancreatic resection for metastatic renal cell carcinoma: presentation, treatment, and outcome.

BACKGROUND: The diverse natural history of renal cell carcinoma (RCC) includes metastases to the pancreas, a very unusual site for distant spread of other cancers. Considering the relatively indolent behavior of some cases of metastatic RCC, pancreatic resection is offered to select patients. METHODS: We reviewed the records of patients at three affiliated university hospital centers who had prior nephrectomy for RCC and subsequent pancreatic resection of metastases. RESULTS: Fourteen patients--9 women and 5 men with a median age of 63.8 years--underwent a total of 15 pancreatic resections for metastatic RCC. Nine (64%) had solitary metastases. The median interval from nephrectomy to diagnosis of pancreatic metastases was 83 months. The median size of metastases was 4.6 cm. There was one perioperative death. Pancreatic recurrence occurred in five patients (36%), and one patient underwent repeat resection. At a median follow-up of 32 months, seven patients (50%) are alive without evidence of disease, and four patients (28%) are alive with recurrent disease. CONCLUSIONS: Resection of pancreatic metastases from RCC is associated with long-term survival and should be considered for patients in whom complete resection is possible.

Surgical treatment of incidentally identified pancreatic masses.

INTRODUCTION: With the improved quality and widespread availability of diagnostic abdominal imaging, incidental intra-abdominal lesions (incidentalomas) are being increasingly identified. Our objective was to characterize the clinical features of asymptomatic patients with incidentally discovered pancreatic lesions and to assess the accuracy of preoperative radiologic diagnosis against the final histologic diagnosis. METHODS: This cohort study is based on prospectively collected data from a surgical pancreatic database. Preoperative imaging of patients with pancreatic incidentalomas was retrospectively and independently assessed by 2 radiologists blinded to the final histologic diagnosis. Seven patients who were asymptomatic and had incidentally discovered pancreatic masses underwent complete resection of the mass. The clinical features and patient survival data were analyzed. The accuracy of preoperative imaging was assessed by comparing the preoperative diagnosis to the final histologic diagnosis. RESULTS: Lesions most commonly occurred in females (6 patients) and in the tail or body of the pancreas (5 patients). The histologic type of the masses included neuroendocrine tumour (3), serous cystadenoma (2), intraductal papillary mucinous tumour (1) and papillary cystic and solid tumour (1). Preoperative imaging was unreliable in predicting the histologic type of the resected mass. CONCLUSIONS: Our findings suggest that preoperative imaging does not always predict the surgical histologic type of pancreatic incidentalomas. Unless the diagnosis of serous cystadenoma is certain, surgical resection should be considered in low-risk patients in whom pancreatic masses are found incidentally.

Multimodal CME for surgeons and pathologists improves colon cancer staging.

BACKGROUND: Optimal treatment of localized colorectal cancer (CRC) depends on accurate retrieval and assessment of lymph nodes (LN) in the resected specimen. METHODS: Formal CE, informal opinion leadership and reinforcing strategies aimed at pathologists and surgeons to improve LN assessment were implemented. RESULTS: In the pre-intervention period a median of 8 lymph nodes were assessed in making a designation of Stage II CRC (n = 115). Thirty months later (post-intervention period) the median number of LN reported in Stage II CRC increased to 18 (n = 41), p < 0.001. CONCLUSION: A durable improvement in staging was realized through a multipronged change initiative aimed at both surgeons and pathologists.

Microsatellite instability as a prognostic factor in resected colorectal cancer liver metastases.

BACKGROUND: Two distinct genetic mutational pathways characterized by either chromosomal instability or high-frequency microsatellite instability (MSI-H) are currently recognized in the pathogenesis of colorectal cancer (CRC). Recently, it has been shown that patients with primary CRC that displays MSI-H have a significant, stage-independent, multivariate survival advantage. Untreated CRC hepatic metastases are incurable and are associated with a median survival of 4 to 12 months. Conversely, surgical resection in selected patients results in a 20% to 50% cure rate. The aim of this study was to investigate the prognostic importance of MSI-H in patients undergoing resection of hepatic CRC metastases. METHODS: DNA was extracted from paraffin-embedded, resected metastatic CRC liver lesions and corresponding normal liver parenchyma from 190 patients. MSI-H status was determined by polymerase chain reaction-based evaluation of the noncoding mononucleotide repeats BAT-25 and BAT-26. RESULTS: MSI was detected in tumors from 5 (2.7%) of the 190 CRC patients. All MSI-H tumors were in patients with node-positive CRC primary tumors. The median survival after hepatic resection of MSI-H and non-MSI-H tumors was 67 and 61 months, respectively (P = .9). CONCLUSIONS: These data suggest that MSI-H is not a common feature in resected CRC liver metastases and do not suggest a role for MSI in stratifying good versus poor prognosis in these patients.