A novel scoring system predicts postsurgical survival and adjuvant chemotherapeutic benefits in patients with pancreatic adenocarcinoma: Implications for AJCC-TNM staging

Background

We evaluated the application of the latest 8^th American Joint Committee on Cancer (AJCC) staging system in Chinese patients and determined whether the addition of biologic markers could improve the prediction of postsurgical survival in pancreatic adenocarcinoma (PC).

Proposal for modification of the ENSAT staging system for adrenocortical carcinoma using tumor grade

Purpose  

Various staging systems for adrenocortical carcinoma (ACC) have been proposed. We hypothesized that incorporating tumor grade into the current European Network for the Study of Adrenal Tumors (ENSAT) staging system would improve the ability to more accurately predict time to recurrence and death.     

Combined expression of S100A4 and Annexin A2 predicts disease progression and overall survival in patients with urothelial carcinoma

ObjectivesTo determine the expression patterns and prognostic value of S100A4 and Annexin A2 for urothelial carcinoma of the urinary bladder.Methods and materialsImmunohistochemical staining for S100A4 and Annexin A2 was performed in 315 archived radical cystectomies and 63 normal specimens. The immunoreactivity of these proteins was correlated to evaluate their clinical significance as prognostic factors.ResultsProtein levels of S100A4 and Annexin A2 were up-regulated in urothelial carcinoma compared with adjacent nontumor tissues. The increased expressions of S100A4 and Annexin A2 were associated with invasion depth, lymph node metastasis, and distant metastasis (P<0.05). High expression of S100A4 correlated with expression of Annexin A2. These alterations in expression were also associated with greater risk of disease progression and decreased chance of carcinoma-specific survival. Further multivariate analysis suggested that expressions of S100A4 and Annexin A2 were independent prognostic indicators for overall survival in urothelial carcinoma. The patients with S100A4-positive/Annexin A2-positive carcinomas presented the lowest 5-year survival rate compared with the other 3 groups.ConclusionsS100A4 and Annexin A2 proteins could be useful prognostic markers to predict tumor progression and prognosis in urothelial carcinoma. The expression patterns of S100A4/Annexin A2 interaction correlated well with the pathologic stage, disease progression, and carcinoma-specific survival. This finding could aid in identifying more biologically aggressive carcinomas and thus patients who might benefit from more intensive adjuvant therapy.     

Bronchioloalveolar carcinoma of the lung: recurrences and survival in patients with stage I disease

OBJECTIVES: The aim of our study was to retrospectively compare the patient characteristics, the frequency and pattern of recurrent disease, and survival in patients with stage I bronchioloalveolar carcinoma and adenocarcinoma of the lung. METHODS: Patients with stage I bronchioloalveolar carcinoma or adenocarcinoma other than bronchioloalveolar carcinoma resected between 1984 and 1992 with adequate clinical follow-up were studied. The clinical characteristics of the patients, extent of initial surgical resection, sites of recurrent disease, and overall survival were examined and compared between the 2 groups. The median follow-up for patients with bronchioloalveolar carcinoma and adenocarcinoma was 6.2 years and 5.9 years, respectively. RESULTS: A total of 138 patients were identified. Thirty-three patients had bronchioloalveolar carcinoma and 105 patients had adenocarcinoma. Eleven (33%) of the patients with bronchioloalveolar carcinoma had never smoked cigarettes versus 9 (9%) of the patients with adenocarcinoma (P =.0036). There were no significant differences between patients with bronchioloalveolar carcinoma and adenocarcinoma in sex distribution and overall recurrence rate. Of the 12 patients with recurrent bronchioloalveolar carcinoma, 1 patient (8%) had extrathoracic disease develop at the site of first recurrence compared with 49% of patients with recurrent adenocarcinoma (P <.001). The 5-year survival in patients with bronchioloalveolar carcinoma and in those with adenocarcinoma was 83% and 63%, respectively (P =.04). CONCLUSIONS: Stage I bronchioloalveolar carcinoma is more likely to occur in nonsmokers. Survival is longer in patients with bronchioloalveolar carcinoma. Further research is warranted to define the etiology, clinical course, and molecular abnormalities in patients with bronchioloalveolar carcinoma to generate more effective therapeutic approaches.     

Sentinel lymph node surgery for staging of breast carcinoma in patients with lymphoproliferative disease

There are few reports confirming the validity of sentinel lymph biopsy in patients with a background of lymphoproliferative disease. We reviewed nine cases of women who underwent sentinel lymph node (SLN) surgery for staging of primary breast cancer with a diagnosis of lymphoproliferative disease. SLN identification rate was 100 per cent with a background of lymphoma in the sentinel node in eight of the nine patients. With a mean follow-up of 37 months, there have been no axillary recurrences in any of these patients. These cases illustrate that SLN staging is feasible and provides axillary staging information in women with breast cancer despite synchronous lymphoproliferative disease.     

Lymphovascular invasion independently predicts increased disease specific survival in patients with transitional cell carcinoma of the upper urinary tract

PURPOSE: We investigated the prognostic impact of lymphovascular invasion (LVI) and traditional prognostic factors for survival in a large series of patients treated surgically for upper tract transitional cell carcinoma (TCC). We also developed a prognostic factors-based model for risk stratification of upper tract TCC. MATERIALS AND METHODS: We identified a study population of 173 consecutive patients treated surgically for upper tract TCC at our institution between 1980 and 2002. We compared LVI with other pathological features and determined the disease specific survival rate. RESULTS: LVI was found in 52 patients (30.1%). As tumor grade and pathological stage increased, the incidence of LVI increased significantly. LVI was found in 12 of 133 patients (9.0%) without lymph node metastasis compared with 40 of 40 patients (100%) with lymph node metastasis. Five and 10-year disease specific survival rates were 84.9% and 80.4% in the absence of LVI, and 40.2% and 21.1% in the presence of LVI, respectively (p <0.001). In multivariate analysis LVI, pathological T stage and tumor grade were independent predictors for disease specific survival. The relative risk of death could be expressed with the formula, exp(0.729 x tumor grade + 1.659 x pathological T stage + 1.160 x LVI). Using this equation the patients were stratified into low risk (grade 1 or 2, LVI negative, stage pT2 or lower), high risk (any tumor grade, LVI positive, stage pT3 or greater) and intermediate risk (all others) groups with significant differences in survival. Five and 10-year disease specific survival rates were 93.0% and 89.4% in the low risk group (82 patients), 66.8% and 62.9% in the intermediate risk group (53 patients), and 25.6% and 0% in the high risk group (38 patients), respectively. CONCLUSIONS: In addition to pathological stage and tumor grade, LVI is an independent prognostic factor for disease specific survival in upper tract TCC. Patients in the high and/or intermediate risk groups may benefit from integrated therapies with surgery and postoperative systemic chemotherapy.     

HBsAg阳性患者原发性肝细胞癌生存分析

目的 探讨HBsAg阳性患者的原发性肝细胞癌(hepatocellular carcinoma,HCC)生存影响因素及评估不同HCC分期系统预测能力.方法 回顾性分析川北医学院附属医院2000年1月至2010年2月收治的HBsAg阳性HCC患者的临床资料.COX比例风险模型行生存的单因素和多因素分析.ROC曲线评估各HCC分期系统预测能力.结果 本组患者1、2、3和5年总体生存率分别为21.3％(165/775),9.4％(73/775),4.9％(38/775)和1.7％(13/775),中位生存4.2个月(0.1 ～148.6个月).多因素分析显示肝硬化程度(B=4.519)、治疗方式(B=4.888)、ALT≥ 2N(B=4.068)、合并门静脉癌栓(B=0.537)、自发性破裂类型(B =5.033)和合并下腔静脉癌栓(B=7.049)是HBsAg阳性HCC总体生存的影响因素.各HCC分期系统均有预测能力,但NSMCS评分(NorthSichuan Medical College Score,NSMCS)优于其他系统,AUC(Area Under the ROC Curve)为0.801(95％ CI0.761 ～0.840),NSMCS≥-2时,灵敏度78.8％,特异度69.3％.不同风险等级中位生存时间差异明显(13.6、3.4和1.3个月,x2=467.636,P=0.000,Log-rank检验).结论 HBsAg阳性HCC总体生存影响因素众多,现行HCC分期系统仍需改进以提高预测能力.     

A novel prognostic nomogram is more accurate than conventional staging systems for predicting survival after resection of hepatocellular carcinoma

BACKGROUND: Prediction of survival after resection of hepatocellular carcinoma (HCC) remains difficult. Numerous staging systems have been devised for purposes of risk classification; we sought to identify the optimal staging system to predict postoperative survival. STUDY DESIGN: One hundred eighty-four patients who underwent primary complete resection of HCC at our institution between 1989 and 2002 were classified according to 8 contemporary staging systems. The ability of these systems to predict relative survival for randomly selected pairs of patients was quantified using the Harrel's concordance index. A novel prognostic nomogram was constructed using prognostically relevant variables. RESULTS: After a median followup of 46 months for surviving patients, the median overall survival was 38 months. The concordance indices for the existing staging systems ranged from 0.54 to 0.59. Only the 2002 American Joint Commission on Cancer system demonstrated a concordance index with a 95% confidence interval exceeding 0.5, indicating that the ability of conventional systems to predict relative survival of randomly selected pairs of patients was generally no better than chance. We developed a novel nomogram based on patient age, serum alpha-fetoprotein level, operative blood loss, resection margin status, tumor size, satellite lesions, and vascular invasion. The nomogram demonstrated a markedly superior concordance index of 0.74 (95% CI, 0.68 to 0.80). A separate nomogram for prediction of recurrence-free survival was also generated. CONCLUSIONS: Contemporary staging systems for HCC do not accurately predict postoperative outcomes. Our prognostic nomogram provides a mechanism for accurate prediction of survival and risk stratification and will require validation at other hepatobiliary centers.     

Association of tumor size and surgical approach with oncological outcomes and overall survival in patients with adrenocortical carcinoma

ObjectivesTo investigate the association of surgical approach with outcomes in patients with adrenocortical carcinomas smaller and larger than 6 cm in size.MethodsWe reviewed the national cancer database for patients undergoing minimally invasive adrenalectomy (MIA) and open adrenalectomy (OA) from 2010 to 2017. To adjust for differences between patients undergoing MIA and OA, we performed propensity score matching within each size strata of ≤6 cm, 6.1 to 10 cm, and 10.1 to 20 cm. We fit generalized estmiating equations with a logit link function to assess for the association of surgical approach with positive surgical margins and a Cox proportional hazards model to assess for the association of surgical approach with overall survival.ResultsWe identified 364 patients that underwent MIA (182) and OA (182) in the matched cohort.  We noted 21% and 18% of patients undergoing MIA and OA had a positive surgical margin, respectively. We did not identify a significant association between surgical approach and positive surgical margins in the cohort as a whole or within each of strata. Furthermore, we did not appreciate a significant association between surgical approach and overall survival in the cohort as a whole or within each size strata.ConclusionIn the National Cancer Database, patients undergoing MIA had similar positive surgical margins and overall survival compared with OA for masses ≤6 cm, 6.1 to 10cm, and >10 cm in size. Patients undergoing MIA should be carefully selected with surgical oncologic integrity being the primary determinants of surgical approach.     

A new staging system for hepatocellular carcinoma associated with portal vein tumor thrombus

BackgroundA new staging system for patients with hepatocellular carcinoma (HCC) associated with portal vein tumor thrombus (PVTT) was developed by incorporating the good points of the BCLC classification of HCC, and by improving on the currently existing classifications of HCC associated with PVTT.MethodsUnivariate and multivariate analysis with Wald χ² test were used to determinate the clinical prognostic factors for overall survival (OS) in patients with HCC and PVTT in the training cohort. Then the conditional inference trees analysis was applied to establish a new staging system.ResultsA training cohort of 2,179 patients from the Eastern Hepatobiliary Surgery Hospital and a validation cohort of 1,550 patients from four major liver centers in China were enrolled into establishing and validating a new staging system. The system was established by incorporating liver function, general health status, tumor resectability, extrahepatic metastasis and extent of PVTT. This staging system had a good discriminatory ability to separate patients into different stages and substages. The median OS for the two cohorts were 57.1 (37.2–76.9), 12.1 (11.0–13.2), 5.7 (5.1–6.2), 4.0 (3.3–4.6) and 2.5 (1.7–3.3) months for the stages 0 to IV, respectively (P<0.001) in the training cohort. The corresponding figures for the validation cohort were 6.4 (4.9–7.9), 2.8 (1.3–4.4), 10.8 (9.3–12.4), and 1.5 (1.3–1.7) months for the stages II to IV, respectively (P<0.001). The mean survival for stage 0 to 1 were 37.6 (35.9–39.2) and 30.4 (27.4–33.4), respectively (P<0.001).ConclusionsA new staging system was established which provided a good discriminatory ability to separate patients into different stages and substages after treatment. It can be used to supplement the other HCC staging systems.     

Prognosis and survival in resected lung carcinoma based on the new international staging system

A new TNM staging system was proposed and the previous system has been revised recently. To evaluate the new TNM staging system for lung cancer, we analyzed records of 1737 patients who underwent pulmonary resection at the National Cancer Center Hospital, Tokyo. With regard to clinical stages, three patients had occult carcinoma; 821 patients had stage I disease; 248 patients, stage II; 465 patients, stage IIIA; 82 patients, stage IIIB; and 118 patients, stage IV. The 5-year survival rates for the respective stages were 50.1% for stage I, 31.2% for stage II, 20.2% for stage IIIA, 5.1% for stage IIIB, and 7.9% for stage IV. In terms of postoperative stages, four patients were classified in stage 0, 536 in stage I, 221 in stage II, 559 in stage IIIA, 159 in stage IIIB, and 258 in stage IV. The 5-year survival rates were as follows: stage I, 65.0%; stage II, 42.9%; stage IIIA, 22.2%; stage IIIB, 5.6%; and stage IV, 7.5%. In both the clinical stage and the postoperative stage, there were significant prognostic differences between stage I and stage II, stage II and stage IIIA, and stage IIIA and stage IIIB, but there was no significant difference in 5-year survival rates between stage IIIB and stage IV.     

European system for cardiac operative risk evaluation predicts long-term survival in patients with coronary artery bypass grafting.

OBJECTIVE: To evaluate the accuracy of predicting long-term mortality in patients with coronary artery bypass grafting (CABG) by using the European system for cardiac operative risk evaluation (EuroSCORE). METHODS: Medical records of patients with CABG (n=3760) between January 1992 and March 2002 were retrospectively reviewed and their predicted surgical risk was calculated according to the standard (study A) and logistic (study B) EuroSCORE. In study A the patients were divided into six groups: 0-2 (n=610), 3-5 (n=1479), 6-8 (n=1099), 9-11 (n=452), 12-14 (n=103) and >14 (n=17). In study B the patients were divided into seven groups: 0.00-2.00 (n=447), 2.01-5.00 (n=1190), 5.01-10.00 (n=890), 10.01-20.00 (n=686), 20.01-30.00 (n=234), 30.01-60.00 (n=254) and >60.00 (n=59). Long-term survival was obtained by the National Death Index and Kaplan-Meier curves were constructed and compared employing the log-rank test. Multivariate Cox regression analysis was performed in order to control for pre, intra and postoperative factors and adjusted hazard ratios were calculated for standard and logistic EuroSCORE groups. The receiver operating characteristic (ROC) curves were plotted to assess the discrimination ability of the EuroSCORE. RESULTS: In study A there were differences among the six groups in 30-day mortality (0.7%, 1.0%, 3.1%, 4.6%, 13.6% and 23.5%; P<0.001), in major complications (8.5%, 10.4%, 16.2%, 20.4%, 31.1% and 35.3%; P<0.001) as well as in actuarial long-term survival (86.2%, 79.6%, 53.6%, 37.9%, 24.9% and 0% from EuroSCORE 0-2 to >14; P<0.001). In study B there were differences among the seven groups in 30-day mortality (0.9%, 1.1%, 1.2%, 3.6%, 3.4%, 8.7% and 15.3%; P<0.001), major complications (8.5%, 10.1%, 12.1%, 18.4%, 16.2%, 26.0% and 30.5%; P<0.001) as well as in actuarial long-term survival (89.5%, 79.9%, 66.9%, 51.0%, 40.3%, 38.4% and 13.7% from EuroSCORE 0.00-2.00 to >60.00; P<0.001). Multivariate Cox regression analysis confirmed that EuroSCORE (standard or logistic) was a statistically significant predictor for long-term mortality, while the area under the ROC curve was 0.72 for either standard or logistic EuroSCORE. CONCLUSION: The predicted surgical risk in CABG patients as calculated by standard or logistic EuroSCORE is a strong predictor for long-term survival in addition to predicting operative survival for which it was originally designed.     

Recurrent or metastatic disease in select patients with adrenocortical carcinoma. Aggressive resection vs chemotherapy.

In a retrospective, nonrandomized comparison of patients with first recurrence of adrenocortical cancer, 18 patients were treated with chemotherapy (primarily mitotane) and 15 patients were treated with surgical resection plus similar chemotherapy. Surgical resection of recurrent adrenocortical cancer was often extensive, with morbidity in 20% of patients and no mortality. Mitotane therapy was ineffective at controlling tumor growth. Median survival from the time of diagnosis for all patients was only 23 months and no patient was cured. Disease-free interval greater than 12 months was associated with prolonged survival, but it only occurred in six patients (18%), with a similar frequency in both treatment groups. Surgical resection of recurrent disease was associated with prolonged survival from the time of first recurrence. The potential benefit of this resection was evident in the 5 patients (33%) who were able to live greater than 5 years from the time of first recurrence with improvement in symptoms and signs of hypercortisolism. Although no patient with recurrent adrenal cancer could be cured, resection of recurrent disease was associated with a slight prolongation of survival and good palliation of Cushing's syndrome.