Neoadjuvant Chemotherapy with Bevacizumab May Improve Outcome after Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Colorectal Carcinomatosis

Background

In selected patients with colorectal peritoneal carcinomatosis (PC), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) may improve survival. We aimed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population.

Methods

Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin (200–460 mg/m²) or mitomycin C (35 mg/m²). Postoperative outcome and long-term survival were prospectively recorded. The impact of clinical variables on overall survival (OS) was assessed using univariate and Cox multivariate analysis.

Results

Between October 2002 and May 2012, 166 patients were treated with CRS and HIPEC. Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients. Postoperative mortality and major morbidity were 2.4 and 35 %, respectively. Half of the patients received adjuvant chemotherapy. After a median follow-up of 18 months, OS was 27 months (95 % confidence interval 20.8–33.2). On univariate analysis, OS was associated with extent of disease (P < 0.001), neoadjuvant chemotherapy with bevacizumab (P = 0.021), completeness of cytoreduction (CC) (P < 0.001), and adjuvant chemotherapy (P = 0.04), but not with primary disease site, synchronous presentation, or chemoperfusion drug. In multivariate Cox regression, independent predictors of OS were CC (hazard ratio 0.29, P < 0.001) and neoadjuvant therapy containing bevacizumab (hazard ratio 0.31, P = 0.019).

Conclusions

Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab. This regimen merits prospective study in patients with resectable PC of colorectal origin.     

Selection Criteria for Postmastectomy Radiotherapy in T1–T2 Tumors with 1 to 3 Positive Lymph Nodes

Background

Postmastectomy radiotherapy (PMRT) is well established in patients with ≥4 positive axillary lymph nodes (ALN); indications in 1 to 3 positive ALN remains controversial. We examined clinicopathologic criteria used for PMRT selection and compared locoregional recurrence (LRR), recurrence-free survival (RFS), and overall survival (OS) among patients with and without PMRT.

Methods

Between 1995 and 2006, a total of 1,331 patients with T1–T2 tumors and 1 to 3 positive ALN underwent mastectomy. We excluded T3/T4 tumors and neoadjuvant chemotherapy; we analyzed 1,087 patients (924 without PMRT, 163 with PMRT). Chi square testing compared clinicopathologic features between groups. The Kaplan–Meier method and Cox regression analysis examined the association between PMRT and LRR, RFS, and OS.

Results

PMRT patients were more likely to be ≤50 years old (p = 0.001) and to have larger tumors (p = 0.01), disease of a higher histologic grade (p = 0.03), lymphovascular invasion (LVI) (p < 0.0001), a greater number of positive ALN (p < 0.0001), extranodal invasion (p < 0.0001), and macroscopic ALN metastases (p < 0.0001). With a median follow-up of 7 years, PMRT and no-PMRT groups were similar in LRR (p = 0.57), RFS (p = 0.70), and OS (p = 0.28). On multivariate analysis of the no-PMRT group, age ≤50 years (p = 0.002) and presence of LVI (p < 0.0001) were associated with LRR. Stratified by age and LVI, patients ≤50 years old and with LVI had the highest 5-year LRR, 10.1 versus 1.1 %, than in patients >50 years old without LVI (p < 0.001).

Conclusions

By using clinicopathologic features, clinicians delivered PMRT to a select group of patients with T1–T2 tumors and 1 to 3 positive ALN, resulting in similarly low rates of 5-year LRR. Among patients not receiving PMRT, age ≤50 years and LVI were associated with increased LRR rates and warrant PMRT consideration.     

Neoadjuvant Radiotherapy for Rectal Cancer: Adherence to Evidence-Based Guidelines in Clinical Practice

Background

Implementation of evidence-based standards is problematic. Level 1 evidence, largely predicated on the German Rectal Cancer Study, supports neoadjuvant treatment for patients with stage II/III rectal cancer. The purpose of this study was to determine to what extent this evidence has affected clinical practice.

Methods

Stage II/III rectal cancer patients undergoing surgery from 1998 to 2007 were identified in the SEER tumor registry. Variables were analyzed with SPSS software. Trends were evaluated with regression models. Survivals were compared with the log-rank test.

Results

A total of 22,136 patients were identified and 15,021 (67.8 %) were treated with adjuvant radiotherapy. A large percentage were >60 years old (64.4 %), white (83.0 %), male (58.8 %), at stage III (55.1 %), and treated with neoadjuvant radiotherapy (35.5 %). A significant increase in the use of neoadjuvant radiotherapy occurred: from 17 % in 1998 to 51 % in 2007 (p < 0.001). Scatter-plot best-fit lines for neoadjuvant and adjuvant radiotherapy intersected at approximately year 2002. Significant increases in preoperative radiotherapy were observed for all races and cancer stages (p < 0.001). On unadjusted analysis, race (p = 0.018), sex (p < 0.001), year of diagnosis (p < 0.001), age (p < 0.001), and stage (p < 0.001) were associated with increased likelihood of neoadjuvant radiotherapy. On logistic regression analysis, male sex [odds ratio (OR) 1.14, p < 0.001), year (OR 1.223, p < 0.001), and stage II (OR 1.39, p < 0.001) were predictors of neoadjuvant therapy.

Conclusions

When adjuvant radiotherapy was utilized, there was rapid adoption of a neoadjuvant approach. This trend predated publication of prospective randomized data.     

Pancreastatin Predicts Survival in Neuroendocrine Tumors

Background

Serum neurokinin A, chromogranin A, serotonin, and pancreastatin reflect tumor burden in neuroendocrine tumors. We sought to determine whether their levels correlate with survival in surgically managed small bowel (SBNETs) and pancreatic neuroendocrine tumors (PNETs).

Methods

Clinical data were collected with Institutional Review Board approval for patients undergoing surgery at one center. Progression-free (PFS) and overall (OS) survival were from the time of surgery. Event times were estimated by the Kaplan–Meier method. Preoperative and postoperative laboratory values were tested for correlation with outcomes. A multivariate Cox model adjusted for confounders.

Results

Included were 98 SBNETs and 78 PNETs. Median follow-up was 3.8 years; 62 % had metastatic disease. SBNETs had lower median PFS than PNETs (2.0 vs. 5.6 years; p < 0.01). Median OS was 10.5 years for PNETs and was not reached for SBNETs. Preoperative neurokinin A did not correlate with PFS or OS. Preoperative serotonin correlated with PFS but not OS. Higher levels of preoperative chromogranin A and pancreastatin showed significant correlation with worse PFS and OS (p < 0.05). After multivariate adjustment for confounders, preoperative and postoperative pancreastatin remained independently predictive of worse PFS and OS (p < 0.05). Whether pancreastatin normalized postoperatively further discriminated outcomes. Median PFS was 1.7 years in patients with elevated preoperative pancreastatin versus 6.5 years in patients with normal levels (p < 0.001).

Conclusions

Higher pancreastatin levels are significantly associated with worse PFS and OS in SBNETs and PNETs. This effect is independent of age, primary tumor site, and presence of nodal or metastatic disease. Pancreastatin provides valuable prognostic information and identifies surgical patients at high risk of recurrence who could benefit most from novel therapies.     

A Multifactorial Histopathologic Score for the Prediction of Prognosis of Resected Esophageal Adenocarcinomas After Neoadjuvant Chemotherapy

Background

For esophageal adenocarcinoma treated with neoadjuvant chemotherapy, postoperative staging classifications initially developed for non-pretreated tumors may not accurately predict prognosis. We tested whether a multifactorial TNM-based histopathologic prognostic score (PRSC), which additionally applies to tumor regression, may improve estimation of prognosis compared with the current Union for International Cancer Control/American Joint Committee on Cancer (UICC) staging system.

Patients and Methods

We evaluated esophageal adenocarcinoma specimens following cis/oxaliplatin-based therapy from two separate centers (center 1: n = 280; and center 2: n = 80). For the PRSC, each factor was assigned a value from 1 to 2 (ypT0-2 = 1 point; ypT3-4 = 2 points; ypN0 = 1 point; ypN1-3 = 2 points; ≤50 % residual tumor/tumor bed = 1 point; >50 % residual tumor/tumor bed = 2 points). The three-tiered PRSC was based on the sum value of these factors (group A: 3; group B: 4–5; group C: 6) and was correlated with patients’ overall survival (OS).

Results

The PRSC groups showed significant differences with respect to OS (p < 0.0001; hazard ratio [HR] 2.2 [95 % CI 1.7–2.8]), which could also be demonstrated in both cohorts separately (center 1 p < 0.0001; HR 2.48 [95 % CI 1.8–3.3] and center 2 p = 0.015; HR 1.7 [95 % CI 1.1–2.6]). Moreover, the PRSC showed a more accurate prognostic discrimination than the current UICC staging system (p < 0.0001; HR 1.15 [95 % CI 1.1–1.2]), and assessment of two goodness-of-fit criteria (Akaike Information Criterion and Schwarz Bayesian Information Criterion) clearly supported the superiority of PRSC over the UICC staging.

Conclusion

The proposed PRSC clearly identifies three subgroups with different outcomes and may be more helpful for guiding further therapeutic decisions than the UICC staging system.     

EGFR and TTF-1 Gene Amplification in Surgically Resected Lung Adenocarcinomas: Clinicopathologic Significance and Effect on Response to EGFR-Tyrosine Kinase Inhibitors in Recurred Cases

Background

Gene amplifications are implicated in cancer development and progression. In this study we investigated the clinicopathologic characteristics associated with EGFR or TTF-1 amplification in lung adenocarcinomas and its prognostic significance.

Methods

We analyzed 118 cases of surgically resected primary lung adenocarcinomas. Amplification of the EGFR or TTF-1 gene was evaluated by fluorescence in situ hybridization and correlated with patients’ clinicopathologic features, including disease-free survival (DFS) and overall survival (OS), in all patients and a subset that were TTF-1 positive or had EGFR mutation. Progression-free survival (PFS) also was analyzed among patients with EGFR mutation who had recurred cancer that was treated with EGFR tyrosine kinase inhibitors.

Results

EGFR or TTF-1 gene amplification was an independent poor prognostic factor for DFS in all patients (p = 0.001), in patients with TTF-1 positivity (p = 0.010), and in patients with EGFR mutation (p < 0.001) and for OS in patients with TTF-1 positivity (p = 0.021) and patients with EGFR mutation (p < 0.001). Patients with TTF-1 amplification had a shorter PFS following EGFR TKI treatment (p = 0.040).

Conclusions

EGFR or TTF-1 gene amplification was a predictive factor for poor prognosis in terms of DFS and OS, especially in patients with TTF-1 positivity or EGFR mutation. Our results also suggested that TTF-1 amplification might be a predictive marker of poor response to EGFR-TKI therapy in patients with recurrent tumor after surgical resection.     

Analysis of Prognostic Factors Impacting Oncologic Outcomes After Neoadjuvant Tyrosine Kinase Inhibitor Therapy for Gastrointestinal Stromal Tumors

Background

Management of gastrointestinal stromal tumors (GISTs) has been transformed with tyrosine kinase inhibitors (TKIs). While data on optimal duration of adjuvant imatinib remains elusive, guidelines for administration of neoadjuvant TKIs remain unknown.

Methods

Under an institutional review board-approved protocol, patients at our institution with a diagnosis of GIST treated with neoadjuvant TKIs and surgical resection were identified. Clinical and pathologic characteristics were obtained from medical records.

Results

Ninety-three patients underwent surgical resection after neoadjuvant TKI therapy; 41 had primary and 52 had recurrent/metastatic GIST. Median follow-up was 2.4 years. Median duration of neoadjuvant therapy was 315 (range 3–1,611) days for primary and 537 (range 4–3,257) days for recurrent/metastatic GIST (p = 0.001). Two-year, recurrence-free survival (RFS) was 85 and 44 % for primary and recurrent/metastatic disease, respectively, whereas 2-year overall survival (OS) was 97 % for primary and 73 % for recurrent/metastatic GIST. For primary GIST, duration of neoadjuvant therapy >365 days (p = 0.02) was associated with higher risk of recurrence on univariate analysis, whereas none of the clinicopathologic factors impacted OS. For recurrent/metastatic disease, disease progression was associated with a shorter OS (p = 0.001), but no factors were found to impact RFS. Lastly, when examining all patients, KIT mutations (p = 0.03) and multivisceral resection (p = 0.011) predicted shorter RFS.

Conclusions

Neoadjuvant TKIs can be effectively used for the treatment of primary and recurrent/metastatic GIST. While duration of neoadjuvant therapy, KIT mutation status, and the need for multivisceral resection can help to predict higher risk for recurrence, progression on neoadjuvant TKIs can aid in selection of patients with recurrent/metastatic disease for surgical resection.     

The Role of Surgical Resection Following Imatinib Treatment in Patients with Recurrent or Metastatic Gastrointestinal Stromal Tumors: Results of Propensity Score Analyses

Background

Although benefits of surgical resection of residual gastrointestinal stromal tumors (GISTs) after imatinib therapy have been suggested, those benefits over imatinib alone have not been proven. We compared the clinical outcomes of surgical resection of residual lesions after imatinib treatment (S group) with imatinib treatment alone (NS group) in patients with recurrent or metastatic GISTs.

Methods

A total of 134 patients (42 in the S group, 92 in the NS group) with recurrent or metastatic GIST who had stable disease for more than 6 months after responding to imatinib were included.

Results

There were no statistically significant differences in the baseline characteristics of the S and NS groups except for age and number of peritoneal metastases. The median follow-up period was 58.9 months. Progression-free survival (PFS) and overall survival (OS) were significantly longer in the S group compared with the NS group (median PFS: 87.7 vs. 42.8 months, p = 0.001; median OS: not reached vs. 88.8 months, p = 0.001). Multivariate analysis revealed that S group, female sex, KIT exon 11 mutations, and low initial tumor burden were associated with longer PFS, and S group and low initial tumor burden were associated with a longer OS. Even after applying inverse probability of treatment weighting adjustment, the S group demonstrated significantly better outcomes in terms of PFS (HR 2.326; 95 % confidence interval [CI] 1.034–5.236; p = 0.0412) and OS (HR 5.464; 95 % CI 1.460–20.408; p = 0.0117).

Conclusion

Surgical resection of residual lesions after disease control with imatinib is likely to be beneficial to patients with recurrent or metastatic GISTs.     

Karnofsky Performance Status predicts overall survival,cancer-specific survival,and progression-free survival following radical cystectomy for urothelial carcinoma

Objective

Radical cystectomy (RC) can provide a survival advantage in patients with urothelial carcinoma of the bladder, but not without significant morbidity rates. Whether the ability of preoperative comorbidity or performance status metrics can stratify patients to overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) following RC is unclear. We analyze our RC experience from 2005 to 2010 to assess the prognostic power of American Society of Anesthesiologists (ASA) score, Charlson Comorbidity Index (CCI), and Karnofsky Performance Status (KPS) index as they relate to OS, CSS, and PFS.

Materials and methods

A retrospective analysis was performed of 234 patients who underwent RC between January 2005 and December 2010; of these, 148 patients had sufficient data for OS, CSS, and PFS analysis. Multivariate Cox proportional hazard modeling generated hazard ratios using as independent variables patient age at surgery, gender, ethnicity, preoperative KPS, CCI, and ASA values, pathologic T-staging, the presence of nodal disease, use of radiation therapy, neoadjuvant chemotherapy, and adjuvant chemotherapy. A recursive partition analysis tree divided the population into high- and low-performance groups, and 5-year survival outcomes were evaluated. OS, CSS, and PFS were employed as Kaplan–Meier dependent variables with similar populations comprising high- and low-performance subgroups.

Results

Mean CSS was 46.8 months (95 % CI 43.2–50.4) with a 5-year CSS of 75 % and OS of 69 %. Patient age, pathologic T-stage, and KPS were identified as independent predictors of OS and CSS. Analysis of PFS as the continuous dependent variable identified only KPS as a statistically significant predictor of freedom from radiologic progression. No statistically significant predictive value was identified for nodal disease, neoadjuvant chemotherapy, adjuvant chemotherapy, gender, ethnicity, CCI, or ASA in terms of OS, CCS, or PFS. Patients with a KPS ≤ 80 had a shorter survival than patients with a KPS ≥ 90 in terms of OS, CSS, and PFS (log-rank Mantel–Cox: p < 0.01). For patients with a KPS ≤ 80, ~5-year CSS was 42 %, while for patients with a KPS ≥ 90 the 5-year survival was 81 %. These survival curves can be further stratified based on T-stage where patients with a KPS ≥ 90 and <T2 have a 5-year CSS of 83 %, patients with a KPS ≥ 90 and >T2 have a 5-year CSS of 80 %, whereas patients with a KPS ≤ 80 and >T2 have a ~5-year CSS of 43 % (p < 0.0001).

Conclusions

Our study suggests the use of KPS to have predictive capacity in terms of OS, CSS, and PFS. This information can be used to inform patients’ survival expectations prior to proceeding with radical cystectomy.     

Surgical Cytoreduction and Survival in Appendiceal Cancer Peritoneal Carcinomatosis: An Evaluation of 46 Consecutive Patients

Background

Surgical cytoreduction and intraperitoneal chemotherapy is increasingly accepted as an effective treatment modality for mucinous appendiceal neoplasm. For the majority of patients with low-grade histology, outcomes have been encouraging. The survival of patients with neoplasms of malignant character is protracted and this study was designed to evaluate the effectiveness of this surgical strategy on outcomes.

Methods

Forty-six consecutive patients with mucinous and nonmucinous appendiceal cancer with peritoneal dissemination were studied. Clinicopathological and treatment related factors were obtained from a prospective database. The study’s end points of disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.

Results

The median DFS and OS after cytoreduction were 20.5 and 56.4 months respectively. Five-year overall survival rate was 45%. Five independent factors associated with DFS and OS were identified through a multivariate analysis: age (DFS p = 0.001, OS p = 0.002), completeness of cytoreduction (DFS p = 0.001, OS p = 0.003), previous chemotherapy treatment (DFS p = 0.021), CA 199 levels (DFS p = 0.013), and tumor grade (OS p = 0.005).

Conclusions

Cytoreductive surgery and intraperitoneal chemotherapy may achieve long-term survival in appendiceal malignancies with peritoneal dissemination for which the predictors of outcomes identified through this study may tailor the disease management to commit patients early toward this successful surgical strategy.     

Value of Preoperative Inflammation-Based Prognostic Scores in Predicting Overall Survival and Disease-Free Survival in Patients with Gastric Cancer

Background

This study was designed to identify which are the best preoperative inflammation-based prognostic scores in terms of overall survival (OS) and disease-free survival (DFS) in patients with gastric cancer.

Methods

Between January 2004 and January 2013, 102 consecutive patients underwent resection for gastric cancer at S. Andrea Hospital, "La Sapienza", University of Rome. Their records were retrospectively reviewed.

Results

After a median follow up of 40.8 months (8–107 months), patients’ 1-, 3-, and 5-year OS rates were 88, 72, and 59 %, respectively. After R0 resection, the 1-, 3-, and 5-year DFS rates were 93, 74, and 56 %, respectively. A multivariate analysis of the significant variables showed that only the modified Glasgow prognostic scores (p < 0.001) and PI (p < 0.001) were independently associated with OS. Regarding DFS, multivariate analysis of the significant variables showed that the modified Glasgow prognostic score (p = 0.002) and prognostic index (p < 0.001) were independently associated with DFS.

Conclusions

The results of this study show that modified Glasgow prognostic score and prognostic index are independent predictors of OS and DFS in patients with gastric cancer.     

Hepatic Pedicle Clamping During Hepatic Resection for Colorectal Liver Metastases: No Impact on Survival or Hepatic Recurrence

Background

Hepatic pedicle clamping is often used during liver resection. While its use reduces blood loss and transfusion requirements, the long-term effect on survival and recurrence has been debated. This study evaluates the effect of hepatic pedicle clamping [i.e., Pringle maneuver (PM)] on survival and recurrence following hepatic resection for colorectal liver metastasis (CRLM).

Methods

Patients who underwent R0 resection for CRLM from 1991 to 2004 were identified from a prospectively maintained database. Operative, perioperative, and clinicopathological variables were analyzed. The primary outcomes were disease-free survival (DFS) and liver recurrence (LR). Disease extent was categorized using a well-defined clinical risk score (CRS). Subgroup analysis was performed for patients given preoperative systemic chemotherapy and postoperative pump chemotherapy.

Results

This study included 928 consecutive patients with median follow-up of 8.9 years. PM was utilized in 874 (94 %) patients, with median time of 35 min (range 1–181 min). On univariate analysis, only resection type (p < 0.001) and tumor number (p = 0.002) were associated with use of PM. Younger age (p = 0.006), longer operative time (p < 0.001), and multiple tumors (p = 0.006) were associated with prolonged PM (>60 min). There was no association between DFS, overall survival (OS) or LR and Pringle time. Neither the CRS nor use of neoadjuvant therapy stratified disease-related outcome with respect to use of PM.

Conclusions

PM was used in most patients undergoing resection for CRLM and did not adversely influence intrahepatic recurrence, DFS, or OS.     

HE4 Expression in Plasma Correlates with Surgical Outcome and Overall Survival in Patients with First Ovarian Cancer Relapse

Background

Epithelial ovarian cancer (EOC) remains the main cause of mortality due to gynecological malignancies. Optimal tumor debulking and platinum response are the most important prognostic factors for overall survival (OS) in primary EOC. In the setting of recurrence, the role of cytoreduction is not clear. A critical point is to predict preoperatively the subgroup of patients with optimal surgical outcome. The aim of the study was to analyze the predictive role of HE4 for surgical outcome and platinum response in EOC patients experiencing a first relapse. Secondary aims were the prognostic role of HE4 for OS and progression-free survival (PFS).

Methods

Plasma was obtained before secondary cytoreduction from 73 EOC patients. A total of 66.7 % underwent a total macroscopic tumor clearance; 86.3 % of the patients had disease that responded to platinum therapy. HE4 was detected by enzyme-linked immunosorbent assay. For statistical analysis, the chi-square test, Fisher’s exact test, Kendall’s tau b, and Mann-Whitney U test were used. OS, PFS rates, and respective 95 % confidence intervals (CI) were estimated according to the Kaplan–Meier method.

Results

At a HE4 cutoff value of 250 pMk, a sensitivity of 52 % and a specificity of 93.8 % (p = 0.001, 95 % CI 0.601–0.861) were reached in predicting total macroscopic tumor clearance. Plasma HE4 concentrations together with platinum response were the only independent prognostic factors for OS (p < 0.001, hazard ratio [HR] 18.77, 95 % CI 4.68–75.25; and p = 0.044, HR 3.33, 95 % CI 1.03–10.7, respectively). Together with ascites, HE4 was the only independent predictive factor for surgical outcome (p = 0.029, odds ratio [OR] 7.2, 95 % CI 1.22–42.19 and p = 0.036, OR 10.18, 95 % CI 1.16–88.69, respectively).

Conclusions

HE4 is an independent predictive marker for surgical outcome and OS in patients with recurrent EOC. Larger population studies are needed to validate these results.     

Patterns of Recurrence and Survival After Lymphadenectomy in Melanoma Patients: Clarifying the Effects of Timing of Surgery and Lymph Node Tumor Burden

Background

Melanoma patients with lymph node (LN) metastases have variable survival after lymphadenectomy. This study investigates whether lymphadenectomy at different times in the course of disease progression influences disease-free survival (DFS; time from primary diagnosis to first recurrence after lymphadenectomy), post recurrence survival (PRS; time from first recurrence after lymphadenectomy to death), and overall survival (OS; time from diagnosis to death).

Methods

Between 1992 and 2010, a total of 1,704 patients underwent lymphadenectomy; 502 underwent immediate completion lymphadenectomy (ICL) after positive sentinel node biopsy (SNB), 214 had delayed completion lymphadenectomy (DCL) for regional recurrence after positive SNB with no ICL or after an earlier false-negative SNB, 709 had no SNB and later required delayed therapeutic lymphadenectomy (DTL) for clinically evident metastasis, and 279 had immediate therapeutic lymphadenectomy (ITL) for clinically positive LNs at primary melanoma diagnosis.

Results

Median DFS for ICL, DCL, DTL, and ITL was 68, 48, 82, and 16 months, respectively (p < 0.001). Median PRS for ICL, DCL, DTL, and ITL was 14, 8, 9, and 9 months, respectively (p < 0.001). Median OS for ICL was not reached whilst for DCL, DTL, and ITL it was 71, 101, and 29 months, respectively (p < 0.001). Extranodal spread and tumor, node, metastasis classification system N stage were the only significant prognostic factors for OS within each group. ICL patients had significantly improved DFS (p = 0.005) and OS (p = 0.012) beyond 5 years compared to DTL patients.

Conclusions

Variable outcomes after lymphadenectomy were observed with different timing of surgery and LN tumor burden. ICL patients had the best outcome.     

Revisiting the Concept of Lymph Node Metastases of Pancreatic Head Cancer: Number of Metastatic Lymph Nodes and Lymph Node Ratio According to N Stage

Background

Some suggest that metastatic lymph node ratio (LNR) may be prognostic of survival in patients with pancreatic cancer. However, this phenomenon was confused by inclusion of node-negative patients in the analysis. The present study was designed to evaluate the prognostic impact of metastatic LNR and the absolute number of metastatic LNs in patients resected for pancreatic cancer.

Methods

Data were collected from 398 patients who underwent curative surgery for pancreatic head cancer at Seoul National University Hospital. Long-term survival was analyzed according to LNR and absolute number of metastatic LNs.

Results

Of the patients, 227 (57.0 %) had LN metastasis. The mean numbers of total retrieved and metastatic LNs were 19.5 and 1.9, respectively, and the mean LNR was 0.11. Median overall survival (OS) of patients was significantly higher in N0 than in N1 patients after curative resection (25.4 vs. 14.8 months, p < 0.001). Median OS was significantly lower in patients with 1 than in those with 0 positive LNs (17.3 vs. 25.4 months, p = 0.001). Among N1 patients, those with 0 < LNR ≤ 0.2 had comparable prognosis than those with >0.2 LNR (median OS 17.2 vs. 12.8 months, p = 0.096), and the number of metastatic LNs did not correlate with median OS (p = 0.365).

Conclusions

The presence of a single positive metastatic LN was associated with significantly poorer OS in patients with pancreatic cancer. When LN metastasis was present, the number of metastatic LNs and LNR had limited prognostic relevance.     

Clinical Outcomes for Neuroendocrine Tumors of the Duodenum and Ampulla of Vater:A Population-Based Study

Background

Previous case series report that neuroendocrine tumors (NETs) of the ampulla of Vater have worse overall survival (OS) than NETs in the duodenum. We aimed to compare the OS of patients with ampullary NETs to patients with duodenal NETs.

Methods

This retrospective comparative cohort study used the Surveillance, Epidemiology, and End Results (SEER) registry from 1988 to 2009. OS was evaluated using Kaplan–Meier estimates and Cox proportional hazard regression.

Results

Ampullary NETs (n?=?120) were larger (median size 18 vs. 10 mm, p?<?0.001), higher grade (poorly and undifferentiated tumor 42 % vs. 12 %, p?<?0.001), higher SEER historic stage (distant metastasis 16 % vs. 7 %, p?<?0.001), and more often resected (78 % vs. 60 %, p?<?0.001) than duodenal NETs (n?=?1,360). Median OS was significantly worse for patients with ampullary NETs than with duodenal NETs (98 vs. 143 months, p?=?0.037). Local resection was performed for 50.5 % of the resected ampullary NETs and resulted in similar OS compared to locally resected duodenal NETs (HR 1.37, 95 % CI 0.76–2.48, p?=?0.291).

Conclusions

While ampullary NETs are more advanced at presentation and have worse OS than duodenal NETs, long-term survival is possible with proximal small bowel NETs. For locally resected NETs, OS is similar between ampullary and duodenal NETs.     

Combination of Osteopontin with Peritumoral Infiltrating Macrophages is Associated with Poor Prognosis of Early-Stage Hepatocellular Carcinoma after Curative Resection

Background

Crosstalk between a tumor and the microenvironment plays a key role in tumor progression and metastasis. This study was performed to elucidate the prognostic significance of combining tumor-secreted osteopontin (OPN) with microenvironment-associated peritumoral macrophages (PTMs) in hepatocellular carcinoma (HCC), especially for those with early-stage disease.

Methods

Tissue microarray-based immunohistochemistry was used to investigate OPN and PTMs expression in two independent cohorts consisting of 374 patients with HCC who underwent radical resection. The prognostic value for the two factors alone or in combination was investigated in these patients.

Results

OPN combined with PTMs was an independent prognostic factor for both overall survival (OS; p < 0.0001) and time to recurrence (TTR; p = 0.003) from the learning cohort (n = 96). Their combined value for prognosis was validated in early-stage HCCs using another independent cohort (n = 278; OS, p < 0.001; TTR, p = 0.001). This combination remained significant in HCCs with low α-fetoprotein levels in both cohorts, and was predictive for early recurrence/death risk (<2 years) compared with a single marker. Only OPN+HCCs had a significant correlation of PTMs levels with OS (p = 0.01) or TTR (p = 0.011).

Conclusions

Tumor OPN combined with PTMs is a promising predictor of tumor recurrence and survival in patients with HCC, especially for those with early-stage disease. The interplay of OPN and PTMs represents a new insight into tumor progression and therapeutic targets for HCC.     

Assessment of Short-Term Clinical Outcomes following Salvage Esophagectomy for the Treatment of Esophageal Malignancy: Systematic Review and Pooled Analysis

Background

Combined chemoradiotherapy is increasingly being used as definitive treatment for locoregional esophageal malignancy. Patients with residual or recurrent localized cancer are often selectively considered for salvage esophagectomy (SALV). The aim of this pooled analysis was to compare short-term clinical outcomes from SALV following definitive chemoradiotherapy with those from planned esophagectomy following neoadjuvant chemoradiotherapy (NCRS).

Methods

MEDLINE, EMBASE, Cochrane, trial registries, conference proceedings and reference lists were searched for relevant comparative studies. Primary outcome measures were in-hospital mortality, anastomotic leak and pulmonary complications. Secondary outcomes were length of hospital stay, negative (R0) resection margin, and estimated blood loss.

Results

Eight studies comprising 954 patients; 242 (SALV) and 712 (NCRS) were included. SALV was associated with a significantly increased incidence of post-operative mortality (9.50 vs. 4.07 %; pooled odds ratio [POR] = 3.02; p < 0.001), anastomotic leak (23.97 vs. 14.47 %; POR = 1.99; p = 0.005), pulmonary complications (29.75 vs. 16.99 %; POR = 2.12; p < 0.001), and an increased length of hospital stay (weighted mean difference = 8.29 days; 95 % CI 7.08–9.5; p < 0.001). There were no significant differences between the groups in the incidence of negative resection margins or estimated blood loss.

Conclusions

SALV has poorer short-term outcomes when compared with planned esophagectomy following neoadjuvant chemoradiotherapy. Patients and multidisciplinary tumor boards should be made aware of these differences in outcomes and SALV should be reserved for practice in high-volume institutions.     

Improved Outcomes in the Management of Esophageal Cancer with the Addition of Surgical Resection to Chemoradiation Therapy

Background

For patients with locally advanced esophageal cancer, prospective randomized clinical trials have reported no added value of surgical resection to chemoradiation alone. Using a large regional cancer registry, our objective was to determine whether curative-intent esophageal resection provided a survival advantage in the multimodality management of esophageal cancer.

Materials and Methods

Using the Los Angeles County Cancer Surveillance Program (CSP), we identified all patients with local and regional (i.e., AJCC Stages I–III) esophageal cancer during the years 1988–2006. Clinical and pathologic data included patient demographics, tumor information, indication for surgery, lymph node status, and timing of therapy. Overall survival was assessed by the Kaplan–Meier method, and multivariate Cox-regression analysis was performed.

Results

From CSP, 2233 patients with esophageal cancer were identified. Median survival (MS) of the entire cohort was 13.1 months. We stratified this cohort into patients who received chemoradiation alone (n = 645) and patients who received trimodality therapy (n = 286) (i.e., chemoradiation and surgery). Patients had significantly improved survival with trimodality therapy compared with chemoradiation alone (MS 25.2 vs. 12.3 months, respectively; P < 0.001). The survival advantage with trimodality therapy was observed for patients with squamous cell carcinoma (MS 24.5 vs. 12.8 months, respectively; P < 0.001) and adenocarcinoma (MS 25.9 vs. 10.6 months, respectively; P < 0.001). By multivariate analysis, trimodality therapy was a significant prognostic factor for improved survival in patients with esophageal cancer (hazard ratio [HR] 0.66, 95% confidence interval [95% CI]: 0.56–0.77, P < 0.001).

Conclusions

Our data indicate that surgical resection remains an important component of the multimodality management of esophageal cancer.     

Ten-year Comparison of All-Cause Mortality after Endovascular or Open Repair of Abdominal Aortic Aneurysms: A Propensity Score Analysis

Background

This study aimed to compare the long-term survival after open (OS) or endovascular (EVAR) repair of abdominal aortic aneurysms (AAAs), exploring baseline factors that could affect long-term outcome.

Methods

We identified 774 patients (501 EVAR, 273 OS, during 1996–2004) with data on perioperative risk factors including 37 variables assessed with a standardized patient response instrument. Propensity score was used to adjust for baseline differences between the two cohorts. Matched cohorts survival analysis and Cox multivariate regression were performed.

Results

Median follow-up was 6.95 (interquartile range 4.46–9.27) years. EVAR patients were older [75.0 ± 7.7 (SD) vs. 71.3 ± 8.5 years, p < 0.001] and had a higher rate of previous myocardial infarction (39.3 vs. 25.3 %, p < 0.001), pulmonary disease (25.9 vs. 18.3 %, p = 0.020), and history of malignancy (5.0 vs. 1.8 %, p = 0.039). The 30-day mortality was comparable (1.4 % EVAR, 1.5 % OS). Although the unadjusted survival rate was lower (median survival: 7.4 years EVAR, 8.8 OS, p = 0.011) and early (within 4 years) hazard was higher after EVAR (p = 0.003), no difference in survival was observed after propensity score-matching (p = 0.688) or propensity score-adjusted Cox regression (hazard ratio 1.01, 95 % confidence interval 0.82–1.25, p = 0.911, EVAR vs. OS). There was a trend toward higher hazard later in both groups. A multivariate Cox regression identified age, pulmonary disease, stroke, dialysis, oral anticoagulation, cardiac enlargement, and smoking history as variables associated with poor survival. Lipid-lowering medication was found to be protective.

Conclusions

Over long-term follow-up, survivals after endovascular and open repair of AAA are similar. Baseline patient characteristics are correlated with survival, but whether attention to the modifiable risk factor can alter outcome remains to be defined.