Background Low platelet count is a marker of portal hypertension but is not routinely included in the standard preoperative evaluation of patients with hepatocellular carcinoma (HCC) because it ...pertains to liver function (Child/model for end-stage liver disease MELD score) and tumor burden (Milan criteria). We hypothesized that low platelet count would be independently associated with increased perioperative morbidity and mortality after resection. Study Design Patients treated with liver resection for HCC between January 2000 and January 2010 at 3 institutions were eligible. Preoperative platelet count, Child/MELD score, and tumor extent were recorded. Low preoperative platelet count (LPPC) was defined as <150 × 103 /μL. Postoperative liver insufficiency (PLI) was defined as peak bilirubin >7 mg/dL or development of ascites. Univariate and multivariate regression was performed for predictors of major complications, PLI, and 60-day mortality. Results A total of 231 patients underwent resection, of whom 196 (85%) were classified as Child A and 35 (15%) as Child B; median MELD score was 8. Overall, 168 (71%) had tumors that exceeded Milan criteria and 134 (58%) had major hepatectomy (≥3 Couinaud segments). Overall and major complication rates were 55% and 17%, respectively. PLI occurred in 25 patients (11%), and 21 (9%) died within 60 days of surgery. Patients with LPPC (n = 50) had a significantly increased number of major complications (28% versus 14%, p = 0.031), PLI (30% versus 6%, p = 0.001), and 60-day mortality (22% versus 6%, p = 0.001). When adjusted for Child/MELD score and tumor burden, LPPC remained independently associated with increased number of major complications (odds ratio OR 2.8, 95% confidence intervals CI 1.1 to 6.8, p = 0.026), PLI (OR 4.0, 95% CI 1.4 to 11.1, p = 0.008), and 60-day mortality (OR 4.6, 95% CI 1.5 to 14.6, p = 0.009). Conclusions LPPC is independently associated with increased major complications, PLI, and mortality after resection of HCC, even when accounting for standard criteria, such as Child/MELD score and tumor extent, used to select patients for resection. Patients with LPPC may be better served with transplantation or liver-directed therapy.
Abstract Background Controversy persists regarding the management of patients with IPMN. International consensus guidelines stratify patients into high risk, worrisome, and low risk categories. Study ...Design The medical records of 7 institutions were reviewed for patients that underwent surgical management of IPMN between 2000-2015. Results 324 patients were included in the analysis. 60.4% of patients had main-duct / mixed type, and 39.7% had branch-duct IPMN. The median cyst size was 2.65 cm, while invasive cancer (IC) or high-grade dysplasia (HGD) was present in 42% (n=136). 68.9% of patients with high risk, 40.0% of patients with worrisome, and 24.6% of patients with low risk features exhibited HGD/ IC. Multivariate analysis demonstrated that only one of three high risk features and two of seven worrisome features predicted the presence of HGD/IC. Positive predictive values for HGD/ IC in patients with obstructive jaundice and lymphadenopathy were 0.83 (95% CI = 0.65-0.94) and 0.69 (95% CI= 0.39-0.91), respectively. In the absence of high risk features, HGD/ IC was still present in 57.4% of patients with two or more worrisome features. Regression analysis demonstrated that each additional worrisome factor present was additive in predicting HGD/ IC in a linear fashion (OR 1.39, 95% CI=1.08-1.80, p<0.01). Conclusions These data demonstrate that the current consensus guidelines for surgical resection of IPMN may not adequately stratify and identify patients at risk for having HGD or invasive cancer. Patients with multiple worrisome features, in the absence of high-risk factors, should be considered for resection.
Background Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; ...adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC. Study Design Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated. Results There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow-up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT. Conclusions This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC.
Background The aim of this study was to compare postoperative outcomes of patients with synchronous colorectal liver metastases treated with either simultaneous or staged colectomy and hepatectomy. ...Study Design From July 1997 to June 2008, a review of our 1,344-patient prospective hepato-pancreatico-biliary database identified 230 patients treated surgically for primary adenocarcinoma of the large bowel and synchronous hepatic metastasis. Clinicopathologic, operative, and perioperative data, complications, and grade of complications (grade 1, minor, to grade 5, death) were reviewed to evaluate selection criteria, operative methods, and perioperative outcomes. Chi-square and proportional hazard model were used to evaluate predictors of outcomes. Results Seventy patients underwent simultaneous resection of colon primary and liver metastasis in a single operation; 160 patients underwent staged operations. Simultaneous resections were similar for size (median 4 cm versus 3.7 cm) and number (median 3 cm versus 3 cm) of liver metastases. Major liver resections (≥3 Couinaud segments) were similar between staged and simultaneous (32% versus 33%, respectively), as was type of colectomy (p = 0.2). Complication rates and severity were similar in both groups: 39 of 70 patients (56%) in the simultaneous group experienced 63 complications versus 88 of 160 patients (55%) with 162 complications in the staged group (p = 0.24). Multivariate analysis identified blood transfusion as a predictor of complication (odds ratio 2.98, p = 0.001). Patients having simultaneous resection required fewer days in the hospital (median 10 days versus 18 days, p = 0.001). Conclusions By avoiding a second laparotomy, simultaneous colon and hepatic resection reduces overall hospital stay, with no difference in morbidity and mortality rates or in severity of complications, compared with staged resection. Simultaneous resection is an acceptable option in patients with resectable synchronous colorectal metastasis.
Background As compared with open hepatic lobectomy (OHL), laparoscopic hepatic lobectomy (LHL) carries a substantial learning curve and potential for improved perioperative outcomes. The purpose of ...this analysis was to compare the outcomes of patients undergoing LHL with those of patients undergoing OHL. Methods Analysis of a 1,545-patient prospective hepato-pancreatico-biliary database from January 2000 to June 2009 identified 450 hepatic lobectomy patients, in whom 90 were LHL. A 4:1 case-matched analysis comparing LHL with 360 OHL patients, controlling for age, American Society of Anesthesiologists class, tumor size, histology, and tumor location was performed. Results A total of 450 patients underwent hepatic lobectomy for malignant or benign lesions, with LHL performed in 90 (20%) patients. There was a significant increase in the percentage of LHL performed during 3 intervals of time: 1995 to 1999, 0%; 2000 to 2004, 1%; 2005 to 2009, 24% (p < 0.0001). There were no significant differences in age (60 versus 62 years), American Society of Anesthesiologists class, body mass index (28.1 versus 26.4), size of largest tumor (4.0 cm versus 6.4 cm), location of tumor(s), or number of tumors (1 versus 1) comparing LHL versus OHL, respectively. There were substantial differences in estimated blood loss, Pringle maneuver, transfusion requirements, complications, and length of stay. Proportional hazards model for all 450 patients demonstrated that OHL (odds ratio = 2.5; 95% CI, 1.2−8.7), blood transfusion, and blood loss were all independently associated with increased complications. Conclusions In this prospective evaluation, LHL was associated with substantial improvements in operative time, Pringle maneuver time, blood loss, transfusion requirements, length of stay, and morbidity without compromising resection margins. These results suggest that LHL is appropriate in selected patients with hepatic tumors.
Background Suboptimal operating room (OR) efficiency is a universal complaint among surgeons. Nonetheless, maximizing efficiency is critical to institutional success. Here, we report improvement ...achieved from low-cost, low-technology measures instituted within a tertiary-care academic medical center/Level I trauma center. Study Design Improvements in preadmission testing and OR scheduling, including appointing a senior nurse anesthetist to help direct OR use, were instituted in March 2012. A retrospective review of prospectively maintained OR case data was performed to evaluate time periods before and after program implementation, as well as to assess trends over time. Operating room performance metrics were compared using Mann-Whitney and chi-squared tests. Changes over time were analyzed using linear regression. Results Data including all surgical cases were available for a 36-month period; 10 months (6,581 cases) before program implementation and 26 months afterward (17,574 cases). Dramatic improvement was seen in first-case on-time starts, which increased from 39.3% to 83.8% (p < 0.0001). Additionally, the percent utilization of available OR time demonstrated a steady increase (p < 0.001). After an initial lag, case volume also improved, evident by an increase observed in the 12-month rolling average of cases per month (p < 0.001). The increase in case volume occurred during peak OR time (7 am to 5 pm ), and did not result from adding cases after hours (5 pm to 11 pm ). Conclusions After many years of what seemed an insoluble problem, simple changes fostering collaboration among services, including active management of the OR schedule and transparent data, have resulted in substantial improvement in OR efficiency and case volume.
Background Molecular staging of sentinel lymph nodes (SLNs) may identify patients who are node-negative by standard microscopic staging but are at increased risk for regional nodal recurrence; such ...patients may benefit from completion lymph node dissection (CLND). Study Design In a multicenter, randomized clinical trial, patients with tumor-negative SLNs by standard pathology (hematoxylin and eosin H and E serial sections and immunohistochemistry IHC) underwent reverse transcriptase polymerase chain reaction (PCR) analysis of SLNs for melanoma-specific mRNA. Microscopically negative/PCR+ patients were randomized to observation, CLND, or CLND with high-dose interferon (HDI). For this post-hoc analysis, clinicopathologic features and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were compared between PCR+ patients who underwent CLND vs observation. Microscopic and molecular node-negative (PCR-) patients were included for comparison. Results A total of 556 patients were PCR+: 180 underwent observation, and 376 underwent CLND. An additional 908 PCR- patients were observed. Median follow-up was 72 months. Disease-free survival (DFS) was significantly better for PCR+ patients who underwent CLND compared with observation (p = 0.0218). No statistically significant differences in OS or distant disease-free survival (DDFS) were seen. Regional lymph node recurrence-free survival (LNRFS) was improved in PCR+ patients with CLND compared to observation (p = 0.0065). The PCR+ patients in the observation group had the worst DFS; those with CLND had similar DFS to that in the PCR- group (p = 0.9044). Conclusions Patients with microscopically negative/PCR+ SLN have an increased risk of nodal recurrence that was mitigated by CLND. Although CLND did not affect OS, these data suggest that molecular detection of melanoma-specific mRNA in the SLN predicts a greater risk of nodal recurrence and deserves further study.
Background Multiple methods have been proposed to classify the micrometastatic tumor burden in sentinel lymph nodes (SLN) for melanoma. The purpose of this study was to determine the classification ...scheme that best predicts nonsentinel node (NSN) metastasis, disease-free survival (DFS), and overall survival (OS). Study Design A single reviewer reanalyzed tumor-positive SLN from a multicenter, prospective clinical trial of patients with melanoma ≥1.0 mm Breslow thickness who underwent SLN biopsy. The following micrometastatic disease burden measurements were recorded: Starz classification, Dewar classification (microanatomic location), maximum diameter of the largest focus of metastasis, maximum tumor area, and sum of all diameters. Univariate and multivariate models and Kaplan-Meier analysis were used to evaluate each classification system. Results We reviewed 204 tumor-positive SLNs from 157 patients. On univariate analysis, all criteria except Starz classification were statistically significant risk factors for NSN metastasis. On multivariate analysis, including Breslow thickness, ulceration, age, sex, and NSN status, maximum diameter (using a cut-off of 3 mm) was the only classification system that was an independent risk factor predicting DFS (hazard ratio 2.31, p = 0.0181) and OS (hazard ratio 3.53, p = 0.0005). By Kaplan-Meier analysis, DFS and OS were significantly different among groups using maximum diameter cut-offs of 1 and 3 mm. Conclusions Maximum tumor diameter outperformed other measurements of metastatic tumor burden, including microanatomic tumor location (Dewar classification), Starz classification, maximum tumor area, and sum of all diameters for prediction of survival. Maximum tumor diameter is a simple method of assessing micrometastatic tumor burden that should be reported routinely.
Background Hospital readmission is becoming a quality measure, despite poor understanding of the risks of readmission. This study examines readmission risk factors after major hepatectomy and ...develops a predictive model. Study Design A retrospective review was performed on patients who had undergone major hepatectomy at 1 of 3 academic centers between the years 2000 and 2012. Clinicopathologic and perioperative data were analyzed for risk factors of 90-day readmission using logistic regression. A readmission risk score was developed and validated in a separate validation set to determine its predictive value. Results Of 1,184 hepatectomies performed, 17.3% of patients were readmitted within 90 days. Factors associated with readmission include operative blood loss (odds ratio OR = 1.00; 95% CI, 1.000–1.001), any postoperative complication (OR = 4.3; 95% CI, 1.8–10.4), a major postoperative complication (OR = 5.7; 95% CI, 3.2–10.2), postoperative pulmonary embolism (OR = 12.2; 95% CI, 1.9–78.4), no postoperative blood transfusion (OR = 3.3; 95% CI, 1.7–6.2), surgical site infection (OR = 5.3; 95% CI, 2.9–10.0), and post-hepatectomy hyperbilirubinemia (OR = 1.1; 95% CI, 1.1–1.2). A scoring system based on these risk factors accurately predicted readmission in the validation cohort. A score of >20 points had a positive predictive value of 30.8% and negative predictive value of 95.6%, and a score >50 had a positive predictive value of 50.9% and negative predictive value of 87.7%. This risk score accurately stratifies readmission risk. Conclusions The risk of hospital readmission within 90 days after major hepatectomy is high and is reliably predicted with a novel scoring system.
Background The optimal method for classifying lymph node (LN) status in breast cancer patients is unknown. We sought to determine if LN ratio (LNR) improves axillary staging. Study Design Kentucky ...Cancer Registry data (1996 to 2007) were used to compare LN categorization schemas. Overall survival (OS) was evaluated using the Kaplan-Meier method and log rank tests. Schemas included: LN positive (+) vs negative (−) disease, current American Joint Committee on Cancer (AJCC) staging (0 vs 1 to 3 vs 4 to 9 vs ≥10 LN+), and LNR 0 vs 0.01 to 0.20 vs 0.21 to 0.65 vs >0.65 (LN− vs low, intermediate, and high risk LN+ groups). Results There were 1,436 patients who had complete LN evaluation data: 880 (61.3%) were LN− and 556 (39.6%) were LN+; 309 (21.5%) had 1 to 3 positive LNs, 138 (9.6%) had 4 to 9 positive LNs, and 109 (7.6%) had 10 or more positive LNs. For LN+ patients, the median number of positive LNs was 3; median LNR was 0.23. The median follow-up was 65 months. LN status was associated with 5-year OS (91.3% and 73.3% for LN− and LN+ groups, respectively, p < 0.001). Increasing AJCC pN stage was associated with worse OS (5-year OS 80.5%, 75.3%, and 49.8% for pN1 to N3, respectively, p < 0.001). LNR was also associated with OS (5-year OS of 83.1%, 72.7%, and 52.7% for the low, intermediate, and high risk LN+ groups, respectively, p < 0.001). In subgroup analyses of patients in the 1 to 3 and 4 to 9 LN+ groups, OS was statistically associated with LNR (p = 0.021 and p = 0.016, respectively). On multivariable survival analysis, LNR was associated with OS, independent of AJCC categorization, p = 0.003. Conclusions LNR was associated with OS, regardless of AJCC LN categories.