Long-Term Outcomes Comparing Surgery to Embolization-Ablation for Treatment of Solitary HCC <7 cm

Background

Resection has been the standard of care for patients with solitary hepatocellular carcinoma (HCC). Transarterial embolization and percutaneous ablation are alternative therapies often reserved for suboptimal surgical candidates. Here we compare long-term outcomes of patients with solitary HCC treated with resection versus combined embo-ablation.

Methods

We previously reported a retrospective comparison of resection and embo-ablation in 73 patients with solitary HCC <7 cm after a median follow-up of 23 months. This study represents long-term updated follow-up over a median of 134 months.

Results

There was no difference in survival among Okuda I patients who underwent resection versus embo-ablation (66 vs 58 months, p = .39). There was no difference between the groups in the rate of distant intrahepatic (p = .35) or metastatic progression (p = .48). Surgical patients experienced more complications (p = .004), longer hospitalizations (p < .001), and were more likely to require hospital readmission within 30 days of discharge (p = .03).

Conclusion

Over a median follow up of more than 10 years, we found no significant difference in overall survival of Okuda 1 patients with solitary HCC <7 cm who underwent surgical resection versus embo-ablation. Our data suggest that there may be a greater role for primary embo-ablation in the treatment of potentially resectable solitary HCC.     

Impact of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial on Clinical Management of the Axilla in Older Breast Cancer Patients: A SEER-Medicare Analysis

Background

American College of Surgeons Oncology Group (ACOSOG) Z0011 demonstrated that eligible breast cancer patients with positive sentinel lymph nodes (SLN) could be spared an axillary lymph node dissection (ALND) without sacrificing survival or local control. Although heralded as a “practice-changing trial,” some argue that the stringent inclusion criteria limit the trial’s clinical significance. The objective was to assess the potential impact of ACOSOG Z0011 on axillary surgical management of Medicare patients and examine current practice patterns.

Methods

Medicare beneficiaries aged ≥66 years with nonmetastatic invasive breast cancer diagnosed from 2001 to 2007 were identified from the Surveillance, Epidemiology and End Results-Medicare database (n = 59,431). Eligibility for ACOSOG Z0011 was determined: SLN mapping, tumor <5 cm, no neoadjuvant treatment, breast conservation; number of positive nodes was determined. Actual surgical axillary management for eligible patients was assessed.

Results

Twelve percent (6,942/59,431) underwent SLN mapping and were node positive. Overall, 2,637 patients (4.4 % (2,637/59,431) of the total cohort, but 38 % (2,637/6,942) of patients with SLN mapping and positive nodes) met inclusion criteria for ACOSOG Z0011, had 1 or 2 positive lymph nodes, and could have been spared an ALND. Of these 2,637 patients, 46 % received a completion ALND and 54 % received only SLN biopsy.

Conclusions

Widespread implementation of ACOSOG Z0011 trial results could potentially spare 38 % of older breast cancer patients who undergo SLN mapping with positive lymph nodes an ALND. However, 54 % of these patients are already managed with SLN biopsy alone, lessening the impact of this trial on clinical practice in older breast cancer patients.     

Impact of Adjuvant Radiotherapy on Survival after Pancreatic Cancer Resection: An Appraisal of Data from the National Cancer Data Base

Purpose

The impact of adjuvant radiotherapy for pancreatic adenocarcinoma (PAC) remains controversial. We examined effects of adjuvant therapy on overall survival (OS) in PAC, using the National Cancer Data Base (NCDB).

Methods

Patients with resected PAC from 1998 to 2002 were queried from the NCDB. Factors associated with receipt of adjuvant chemotherapy (ChemoOnly) versus adjuvant chemoradiotherapy (ChemoRad) versus no adjuvant treatment (NoAdjuvant) were assessed. Cox proportional hazard modeling was used to examine effect of adjuvant therapy type on OS. Propensity scores (PS) were developed for each treatment arm and used to produce matched samples for analysis to minimize selection bias.

Results

From 1998 to 2002, a total of 11,526 patients underwent resection of PAC. Of these, 1,029 (8.9 %) received ChemoOnly, 5,292 (45.9 %) received ChemoRad, and 5,205 (45.2 %) received NoAdjuvant. On univariate analysis, factors associated with improved OS included: younger age, higher income, higher facility volume, lower tumor stage and grade, negative margins and nodes, and absence of adjuvant therapy. On multivariate analysis with matched PS, factors independently associated with improved OS included: younger age, higher income, higher facility volume, later year of diagnosis, smaller tumor size, lower tumor stage, and negative tumor margins and nodes. ChemoRad had the best OS (hazard ratio 0.70, 95 % confidence interval 0.61–0.80) in a PS matched comparison with ChemoOnly (hazard ratio 1.04, 95 % confidence interval 0.93–1.18) and NoAdjuvant (index).

Conclusions

Adjuvant chemotherapy with radiotherapy is associated with improved OS after PAC resection in a large population from the NCDB. On the basis of these analyses, radiotherapy should be a part of adjuvant therapy for PAC.     

Inflammatory Markers are Associated with Outcome in Patients with Unresectable Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization

Background

The serum neutrophil–lymphocyte ratio (NLR) is associated with outcomes in several solid organ cancers, including hepatocellular carcinoma (HCC).

Methods

We reviewed our experience in patients with HCC who underwent transarterial chemoembolization (TACE) as the initial treatment. Serum complete blood counts were used to calculate the NLR before and after TACE. The Kaplan–Meier method was used to determine survival and significant differences between groups by the log-rank test.

Results

There were 103 patients identified who underwent TACE for HCC. The median age was 60.5 years. Median overall survival was 12.6 (95 % confidence interval 8.3–17) months. Median survival in patients with a high preprocedural NLR was 4.2 months compared to 15 months in those with a normal NLR (p = 0.021). In those whose NLR either rose 1 month after treatment or remained elevated, survival was worse compared to those who normalized or remained normal (18.6 vs. 10.6 months, p = 0.026). The same was true at 6 months (21.3 vs. 9.5 months, p = 0.002). An unresponsive NLR was associated with very poor outcome (median survival 3.7 months). Multivariate analysis of clinicopathologic factors showed that presence of extrahepatic disease and high NLR were independent factors associated with worse survival.

Conclusions

Our study demonstrates that periprocedural trends of serum NLR are associated with outcome in unresectable HCC undergoing TACE. Serum NLR is easy to calculate from a routine complete blood count with differential. Along with liver function, serum NLR may be helpful to clinicians in providing prognostic information and monitoring response to therapy.     

BRAF V600E Mutation Analysis in Papillary Thyroid Carcinomas by Peptide Nucleic Acid Clamp Real-time PCR

Background

Activating somatic mutation of the BRAF ^V600E has been identified as the most common genetic event in papillary thyroid carcinoma (PTC) with a variable frequency (32–87 %) in different series by different methods. The BRAF ^V600E mutation is associated with various clinicopathological parameters. The mutation is an important factor for the management of the PTC patients. The objective of this study was to detect the BRAF ^V600E mutation in PTCs by peptide nucleic acid (PNA) clamp real-time PCR and to analyze the results with clinicopathological parameters.

Methods

We performed genetic analysis of BRAF ^V600E by PNA clamp real-time PCR in 211 PTCs in Korea, stratified by clinicopathological parameters.

Results

The BRAF ^V600E mutation was detected in 90 % of PTC cases, and it occurred significantly more often in female patients than in male patients (p = 0.001). The clinicopathological parameters of age, tumor size, and disease stage were not associated with the BRAF ^V600E mutation, while extrathyroid invasion (p = 0.031), lymph nodal metastasis (p = 0.002), and tumor multiplicity (p = 0.020) were.

Conclusions

The prevalence (90 %) of the BRAF ^V600E mutation in this study is the highest ever reported, confirming the key role of this mutation in PTC tumorigenesis. The BRAF ^V600E mutation was associated with aggressive clinical behaviors including extrathyroid invasion, lymph nodal metastasis and tumor multifocality. The PNA clamp real-time PCR method for the BRAF ^V600E mutation detection is sensitive and is applicable in a clinical setting.     

Neuroendocrine Tumors of the Colon and Rectum: Prognostic Relevance and Comparative Performance of Current Staging Systems

Background

With increasing interest in neuroendocrine tumors (NETs), three staging systems for NETs of the colon and rectum have been published. Their prognostic relevance has not been examined and compared in an independent clinical database.

Methods

From the National Cancer Database (NCDB), 5457 patients diagnosed with colorectal neuroendocrine tumor (CRNETs) between 1998 and 2002 were staged according to the staging systems from (1) European Neuroendocrine Tumor Society (ENETS, 2006; n = 1537); (2) American Joint Committee on Cancer (AJCC, 2009; n = 1140); and (3) location-specific staging systems from the Surveillance Epidemiology and End Results (SEER, 2008; n = 942). Stage-stratified overall survival (OS) and Cox-specific concordance indices were calculated for each system. Independent prognostic factors were identified by multivariate analysis.

Results

Five-year OS for stage I, II, III, and IV CRNETs as defined by the ENETS staging system were 90.8, 77.3, 53.1, and 14.8 %, respectively. For well-differentiated CRNETs, the 5-year OS for stage I, II, III, and IV as defined by the AJCC staging system were superior: 90.6, 83.9, 64.8, and 24.9 %, respectively. Both staging systems had a concordance index of 0.72. After specifying location in the colon versus rectum, all three systems demonstrated acceptable performance. Histologic grade was a significant independent predictor of OS not currently incorporated in the staging systems.

Conclusions

The three staging systems showed comparable prognostic stratification of CRNETs, while the AJCC and ENETS systems are the most parsimonious. The current analysis supports the use of the AJCC for well-differentiated disease and ENETS systems for all CRNETs until there is further evidence for modification.     

A Collision of Diseases: Chronic Lymphocytic Leukemia Discovered During Lymph Node Biopsy for Melanoma

Background

In the United States in 2012, there were 16,060 new cases of chronic lymphocytic leukemia (CLL). Often CLL is clinically occult and first detected during pathologic evaluation of the sentinel lymph node biopsy (SLNB). We reviewed our experience of patients with the coexisting diagnosis of melanoma and CLL.

Methods

An institutional review board-approved review was performed on patients with CLL and melanoma treated from 1995 to 2009 at Moffitt Cancer Center and compared with the incidence of melanoma and CLL in our tumor registry patients with breast, prostate, lung, and colon cancer.

Results

Fifty-two patients (44 males; median age, 71 years [range, 46–88]) were identified with concurrent diagnoses of melanoma and CLL. Twenty-two patients (42 %) had CLL on SLNB for their melanoma. Thirty-two patients (62 %) were diagnosed with melanoma before CLL. Concomitant or prior cancer diagnoses included nonmelanoma skin cancers (N = 29), prostate (N = 6), colorectal (N = 2), and Merkel cell carcinoma (N = 2). Five of 20 patients (25 %) had metastatic melanoma found at the time of SLNB. Patients with melanoma had a tenfold increase of CLL diagnosis compared with colorectal cancer patients, an eightfold increase compared to prostate cancer patients, and a fourfold increase compared with breast cancer patients.

Conclusions

We have confirmed an increased association of CLL and melanoma. This may be related to an underlying immunologic defect; however, there has been scant investigation into this phenomenon. Surgeons and pathologists should understand this occurrence and recognize that not all grossly enlarged or abnormal sentinel lymph nodes in melanoma patients represent melanoma.     

Blurry Boundaries: Do Epithelial Borderline Lesions of the Breast and Ductal Carcinoma In Situ Have Similar Rates of Subsequent Invasive Cancer?

Background

The histology of epithelial “borderline lesions” of the breast, which have features in between atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), is well described, but the clinical behavior is not. This study reports subsequent ipsilateral breast events (IBE) in patients with borderline lesions compared with those with DCIS.

Methods

Patients undergoing breast-conserving surgery for borderline lesions or DCIS from 1997 to 2010 were identified from a prospective database. IBE was defined as the diagnosis of subsequent ipsilateral DCIS or invasive ductal carcinoma.

Results

A total of 143 borderline-lesion patients and 2,328 DCIS patients were identified. Median follow-up was 2.9 and 4.4 years, respectively. 7 borderline-lesion and 172 DCIS patients experienced an IBE. 5 year IBE rates were 7.7 % for borderline lesions and 7.2 % for DCIS (p = .80). 5 year invasive IBE rates were 6.5 and 2.8 %, respectively (p = .25). Similarly, when analyses were restricted to patients who did not receive radiotherapy, or endocrine therapy, or both, borderline-lesion and DCIS patients did not demonstrate statistically significant differences in rates of IBE or invasive IBE.

Conclusions

When compared with DCIS, borderline lesions do not demonstrate lower rates of IBE or invasive IBE. Despite “borderline” histology, a 5 year IBE rate of 7.7 % and an invasive IBE rate of 6.5 % suggest that the risk of future carcinoma is significant and similar to that of DCIS.     

Predicting Nipple–Areolar Involvement Using Preoperative Breast MRI and Primary Tumor Characteristics

Background

Preoperative assessment of the nipple–areolar complex (NAC) is invaluable when considering nipple-sparing mastectomy. Our hypothesis is that breast magnetic resonance imaging (MRI) may predict involvement of the NAC with tumor.

Methods

Clinical, histopathologic, and imaging data were compiled for patients who underwent preoperative breast MRI followed by mastectomy or nipple-sparing mastectomy for malignancy between 2006 and 2009. Blinded rereview of all MRI studies was performed by a breast MRI imager and compared to initial MRI findings. Multivariate analysis identified variables predicting NAC involvement with tumor.

Results

Of 77 breasts, 18 (23 %) had tumor involving or within 1 cm of the NAC. The sensitivity of detecting histopathologically confirmed NAC involvement was 61 % with history and/or physical examination, and 56 % with MRI. Univariate analysis identified the following variables as significant for NAC involvement: large tumors near the nipple on preoperative MRI, node-positive disease, invasive lobular carcinoma, advanced histopathologic T stage, and neoadjuvant chemotherapy. On multivariate analysis, only tumor size >2 cm and distance from tumor edge to the NAC <2 cm on MRI maintained significance. Pearson correlation coefficient for MRI size compared to histopathologic size was 0.53 (P < 0.0001).

Conclusions

MRI is not superior to thorough clinical evaluation for predicting tumor in or near the NAC. However, MRI-measured tumor size and distance from the NAC are correlated with increased risk of NAC involvement. The combination of preoperative history and physical examination, tumor characteristics, and breast MRI can aid the surgeon in predicting a tumor-involved nipple more than any single modality alone.     

Short-Term Outcomes after Combined Colon and Liver Resection for Synchronous Colon Cancer Liver Metastases: A Population Study

Introduction

The timing of surgical resection for stage IV colon cancer with liver metastasis and the safety of simultaneous colon and liver resection remains controversial. The purpose of our study was to evaluate short-term outcomes after combined colon and liver resection (CCLR) versus colon resection (CR) or liver resection alone (LR) using a population database.

Methods

The National Inpatient Sample was used to select patients who had surgery for colon cancer from 2002 to 2006. We evaluated for in-hospital morbidity, mortality, and prolonged length of stay (PLOS). Our analysis was done using design-weighted unadjusted analysis and logistic regression.

Results

We identified 361,096 patients during our study period (CCLR 3,625; CR 322,286; LR 35,185). CCLR was not associated with an increased risk of complications (odds ratio (OR) 1.12; 95 % confidence interval (CI) 0.94–1.33; P = 0.21) or PLOS (OR 1.19; 95 % CI 0.99–1.4; P = 0.06) compared with CR. In-hospital mortality occurred in 3.5 % of patients who underwent CCLR and was not significantly associated with mortality compared with CR alone (OR 1.17; 95 % CI 0.79–1.74; P = 0.43). Liver lobectomy with CR was associated with a PLOS and a trend toward increased morbidity and mortality. Significant predictors of complications, mortality, and PLOS included: age >70 years, male gender, nonprivate health insurance, and Elixhauser score >1.

Conclusions

CCLR with limited liver resection can be performed with similar morbidity and mortality to colectomy alone. For patients who require hepatic lobectomy, however, strong consideration should be given to a staged approach.