Postablation Stimulated Thyroglobulin Level is an Important Predictor of Biochemical Complete Remission after Reoperative Cervical Neck Dissection in Persistent/Recurrent Papillary Thyroid Carcinoma

Background

The efficacy of reoperative cervical neck dissection (RND) in achieving biochemical complete remission (BCR) (or postreoperation stimulated thyroglobulin [sTg] of <0.5 ng/mL) remains unclear in persistent/recurrent papillary thyroid carcinoma (PTC). We hypothesized that lower postablation sTg levels would indicate a higher rate of BCR after RND. Our study examined the association between postablation sTg and BCR after one or more RNDs.

Methods

Of 199 patients who underwent RND, 81 patients were eligible. The postablation sTg levels (≤2 and >2 ng/mL) were correlated with the postreoperation sTg levels after RNDs. Patients’ clinicopathological characteristics, operative findings, and subsequent RNDs were compared between those with BCR after RNDs and those without.

Results

Those with postablation sTg levels of ≤2 ng/mL had significantly higher BCR rate after the first RND (77.8 vs. 5.6 %, p < 0.001), overall BCR after one or more RNDs (77.8 vs. 9.3 %, p < 0.001), and better 5-year recurrence-free survival after the first RND (80.0 vs. 60.1 %, p = 0.049) than those with postablation sTg levels of >2 ng/mL. Overall BCR gradually decreased after each subsequent RND. Postablation sTg significantly correlated with postreoperation sTg (ρ = 0.509, p < 0.001). After adjusting for the number of metastatic lymph nodes excised at first RND and presence of extranodal extension, postablation sTg of ≤ 0.2 ng/mL was the only independent factor for BCR after one or more RNDs (odds ratio 37.0, 95 % confidence interval 5.68–250.0, p = 0.001).

Conclusions

Only a third of patients who underwent one or more RNDs for persistent/recurrent PTC had BCR afterward. Postablation sTg level was an independent factor for BCR. Completeness of the initial operation is important for the subsequent success of RND.     

Outcomes of Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients Older Than 70 Years; Survival Benefit at Considerable Morbidity and Mortality

Background

Cytoreductive surgery (CRS)/Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is associated with prolonged survival in selected patients with peritoneal surface disease. Yet, for elderly patients (older than 70 years of age) CRS/HIPEC is controversial, due to associated morbidity.

Methods

A retrospective analysis of a prospective database of 950 procedures was performed. Type of malignancy, demographics, performance and resection status, hospitalization, morbidity, mortality, and survival were reviewed.

Results

A total of 81 patients (median age 73, range 70–87) underwent CRS/HIPEC between 1991 and 2011. Median follow-up was 48.1 months. Complete cytoreduction was achieved in 44 %. Median survival was 31.8 months for appendiceal cancer, 41.5 for mesothelioma, 54.0 for ovarian cancer, 13.2 for colon cancer, and 7.6 for gastric cancer. The 30-day mortality was 13.6 %. The combined grade III and IV morbidity was 38 %. Median ICU and hospital stay for uncomplicated patients was 1 and 8 days, respectively. The 3-month mortality was 27.4 %. There were no deaths in the octogenarian group. In stepwise multivariate analysis, type of primary (p = 0.03), albumin (p = 0.02), and R status (p = 0.007) were predictive of survival only in the absence of complications. Splitting the data at the midpoint of surgical experience, there was a drop in 1- and 3-month mortality over time to 9.5 and 19.3 %, respectively, while the median survival increased from 11.2 (N = 39) to 46.9 months (N = 42).

Conclusions

HIPEC in the elderly is associated with a steep learning curve and considerable morbidity and mortality. However, age alone is not a contraindication for the procedure. Institutional experience and stringent patient selection are key factors for prolonged survival.     

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.