Prognostic value of histological grading in ductal adenocarcinoma of the pancreas

Summary A new histological grading system with prognostic correlation for pancreatic cancer was proposed by Kl?ppel et al. in 1985. Histological sections from 60 ductal adenocarcinomas operated on between January 1980 and December 1990 were retrospectively reviewed in order to compare Kl?ppel's grading with standard TNM's grading and assess their prognostic value. Kl?ppel grading was determined through the following histologic and cytologic factors: number duct-like structures, mucus production, neoplastic epithelium, arrangement and pleomorphism of nuclei, and mitotic activity. A score from 0 (well differentiated) to 2 (poorly differentiated) was given to each factor. The mean value obtained dividing the sum of the different values by the number of parameters was used to construct a malignancy scale and therefore allocate each patient to his Kl?ppel grading. The concordance index K between the two grading systems was relevant (K=0.85p<0.001). There was no relation either between gradings (Kl?ppel or TNM) and preoperative duration of symptoms or between gradings and UICC stages. TNM's G2 grades of malignancy, N status, and tumor stage were significantly related to survival time (p<0.05). Kl?ppel's grading does not show any advantage over the classical and simpler TNM's grading, even though it can be considered more objective and therefore more easily reproducible. This characteristic further should be enhanced by the introduction of a malignancy scale such as the “mean value”.     

Prognostic value of the preoperative fibrinogen-to-albumin ratio in pancreatic ductal adenocarcinoma patients undergoing R0 resection

BACKGROUNDInflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival in malignant tumors.AIMTo investigate the prognostic significance of FAR in patients undergoing radical R0 resection of pancreatic ductal adenocarcinoma (PDAC).METHODSWe retrospectively analyzed the data of 282 patients with PDAC who underwent radical R0 resection at The Cancer Hospital of the Chinese Academy of Medical Sciences from January 2010 to December 2019. The surv_cutpoint function of the R package survminer via RStudio software (version 1.3.1073, http://www.rstudio.org) was used to determine the optimal cut-off values of biological markers, such as preoperative FAR. The Kaplan-Meier method and log-rank tests were used for univariate survival analysis, and a Cox regression model was used for multivariate survival analysis for PDAC patients who underwent radical R0 resection.RESULTSThe optimal cut-off value of FAR was 0.08 by the surv_cutpoint function. Higher preoperative FAR was significantly correlated with clinical symptoms (P = 0.001), tumor location (P < 0.001), surgical approaches (P < 0.001), preoperative plasma fibrinogen concentration (P < 0.001), and preoperative plasma albumin level (P < 0.001). Multivariate analysis showed that degree of tumor differentiation (P < 0.001), number of metastatic lymph nodes [hazard ratio (HR): 0.678, 95% confidence interval (CI): 0.509-0.904, P = 0.008], adjuvant therapy (HR: 1.604, 95%CI: 1.214-2.118, P = 0.001), preoperative cancer antigen 19-9 level (HR: 1.740, 95%CI: 1.288-2.352, P < 0.001), and preoperative FAR (HR: 2.258, 95%CI: 1.720-2.963, P < 0.001) were independent risk factors for poor prognosis in patients with PDAC who underwent radical R0 resection.CONCLUSIONThe increase in preoperative FAR was significantly related to poor prognosis in patients undergoing radical R0 resection for PDAC. Preoperative FAR can be used clinically to predict the prognosis of PDAC patients undergoing radical R0 resection.     

Long-term survival after pancreaticoduodenectomy in patients with ductal adenocarcinoma of the pancreatic head

Background: Pancreatic ductal adenocarcinoma(PDAC) has the worst prognosis of all malignant tumors due to unavailable screening methods, late diagnosis with a low proportion of resectable tumors and resistance to systemic treatment. Complete tumor resection remains the cornerstone of modern multimodal strategies aiming at long-term survival. This study was performed to investigate the overall rate of long-term survival(LTS) and its contributing factors. Methods: This was a retrospective single-center analysis of consecutive patients undergoing pancreaticoduodenectomy(PD) for PDAC between 2007 and 2014 at the St. Josef Hospital, Ruhr University Bochum, Germany. Clinical and laboratory parameters were assessed and evaluated for prediction of LTS with Cox regression analysis. Results: The overall rate of LTS after PD for PDAC was 20.4%(34/167). Median survival was 24 months regardless of adjuvant treatment. Carbohydrate antigen 19-9 levels, tumor grade, lymph vessel invasion, perineural invasion and reduced general condition were significantly associated with LTS in univariate analysis( P 0.05). Serum levels of carbohydrate antigen 19-9, American Joint Committee on Cancer stage, tumor grade, abdominal pain, male, exocrine pancreatic insufficiency and duration of postoperative hospital stay were independent predictors of cancer survival in multivariable analysis. Conclusions: Cancer related characteristics are associated with LTS in multimodally treated patients after curative PDAC surgery.     

Original study: The rescue staging for pancreatic ductal adenocarcinoma with inadequate examined lymph nodes

BackgroundIn previous studies, it’s recommended that the lymph node involvement should be evaluated with enough examined lymph nodes (eLNs) in the 8th American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer. This study aims to put forward a rescue staging system for pancreatic ductal adenocarcinoma (PDAC) patients with inadequate eLNs after pancreatoduodenectomy (PD).Method11,224 PDAC patients undergoing PD in The Surveillance, Epidemiology, and End Results (SEER) database were included. Another Ruijin Pancreatic Disease Center (RJPDC) database consisted of 821 patients was utilized for external validation.ResultsThe proportions of patients with eLNs≥15 were 44.7% and 32.8% in SEER and RJPDC database separately. The rescue staging system was put forward relying on LNR (HR = 1.83, 95% CI 1.74–1.92, P < 0.001) for N staging of eLNs<15 population and pLNs for the rest. The TNM modalities were also rearranged in the rescue system for better survival coordination. The C-index of rescue staging system was 0.638 while that of AJCC 8th staging system was 0.613 in SEER database. Similar phenomena were observed in RJPDC database. Kaplan-Meier analyses revealed reliable internal coherences (SEER: Ib: P = 0.26; IIa: P = 0.063; IIb: P = 0.53; IIIa: P = 0.11. RJPDC: Ib: P = 0.32; IIa: P = 0.66; IIb: P = 0.76; IIIa: P = 0.66) and significant staging efficiency (SEER: P < 0.001; RJPDC: P = 0.002).ConclusionA rescue staging system was put forward regardless of the eLNs number. And the novel system manifested better predictive capacity than 8th AJCC staging system.     

Prognostic significance of PINCH signalling in human pancreatic ductal adenocarcinoma

Objective:

Prognostic markers for pancreatic ductal adenocarcinoma (PDA) have failed to accurately predict patient prognosis. Recently, interest has developed in the accuracy of integrin-associated PINCH protein expression in human cancers as a predictive marker of tumour status. The goal of this study was to define the expression of PINCH protein in PDA.

Methods:

Human PDA samples and orthotopic tumours from a murine model were analysed by immunohistochemistry for PINCH expression. In the animal model, PINCH expression was compared between primary and metastatic tumours. In the human samples, PINCH expression was correlated with stage, nodal involvement, margin status and overall survival.

Results:

In the murine model, there was greater PINCH expression in metastatic tumours than in primary tumours. In the human PDA samples, greater staining for PINCH in the tumour cells was correlated with higher T status. Additionally, high PINCH expression in the stroma was associated with decreased overall survival.

Conclusions:

Findings of increased PINCH protein in more advanced stages of human PDA, as well as in metastatic tumours in the animal model, support the hypothesis that PINCH is an important controller of cell survival and migration. Additionally, the importance of the differential expression of PINCH in the human tumour and stroma warrants further evaluation.     

Prognostic value of major pathological response following neoadjuvant therapy for non resectable pancreatic ductal adenocarcinoma

BackgroundThe aim of this study is to evaluate the impact of major pathological response on overall survival (OS) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma following neoadjuvant treatment, and to identify predictors of major pathological response.MethodsPatients surgically resected following neoadjuvant treatment between 2010 and 2020 at the Pederzoli Hospital were retrospectively analyzed. Pathologic response was assessed using the College of American Pathologists (CAP) score, and major pathological response was defined as CAP 0–1. OS was estimated and compared using the Kaplan-Meier method and log-rank test. A logistic and Cox regression model were performed to identify predictors of major pathologic response and OS.ResultsOverall, 200 patients were included in the study. A major and complete pathological response were observed in 52(26.0%) and 15(7.3%) patients respectively. The 1-, 3-, 5-year OS was 92.7, 67.2, and 41.7%, and 71.0, 37.4, and 20.8% in patients with or without major pathologic response respectively (log-rank test p < 0.001). Major pathologic response was confirmed as independent predictor of OS (OR 0.50 95%CI 0.29–0.88, p = 0.01). Post-treatment CA19-9 normalization (OR 4.20 95%CI 1.14–10.35, p = 0.02) and radiological post-treatment tumor residual size<25 mm (OR 2.71 95%CI 1.27–5.79, p = 0.01) were found to be independent predictors of major pathologic response.ConclusionPatients experienced a major pathological response after neoadjuvant treatment have an increased survival, and major pathologic response is an independent predictor of OS. A normal CA19-9 value and radiological tumor size at restaging are confirmed to be independent predictors of major pathologic response.     

胰头癌淋巴结微转移的检出及其分析

目的 通过对胰头癌切除标本中淋巴结微转移的检测,分析淋巴结微转移对胰头痛临床分期及预后的影响,探讨其临床价值.方法 以手术显微镜法完整取出20例冈胰头癌行区域性胰十二指肠切除术标本中的淋巴结,常规病理检测淋巴结转移,免疫组化检测淋巴结微转移.结果 20例标本中共找到677枚淋巴结,常规病理显示13例共87枚淋巴结发生转移.在病理检测阴性的590枚淋巴结中,免疫组化检测又发现3例57枚淋巴结存在微转移.常规病理结合免疫组化检测,淋巴结转移阳性患者从65%(13/20)增加到80%(16/20);转移淋巴结的检出率从12.9%(87/677)上升到21.3%(144/677),相差显著(P<0.05).微转移检测使3例ⅡA期患者转为ⅡB期,有淋巴结微转移患者的1年内肿瘤转移、复发率为75%,而无微转移者的转移、复发率为25%.结论 胰头癌淋巴结微转移的检出有助于肿瘤分期的确定和预后的判断.     

Prognostic assessment of different lymph node staging methods for pancreatic cancer with R0 resection: pN staging,lymph node ratio,log odds of positive lymph nodes

Background and aimsSurvival after surgical resection of pancreatic adenocarcinoma is poor. Several prognostic factors such as the status of the resection margin, lymph node status, or tumour grading have been identified. The aims of the present study were to evaluate and compare the prognostic assessment of different lymph nodes staging methods: standard lymph node (pN) staging, metastatic lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in pancreatic cancer after pancreatic resection.Materials and methodsData were retrospectively collected from 143 patients who had undergone R0 pancreatic resection for pancreatic ductal adenocarcinoma. Survival curves (Kaplan–Meier and Cox proportional hazard models), accuracy, and homogeneity of the 3 methods (LNR, LODDS, and pN) were compared to evaluate the prognostic effects.ResultsMultivariate analysis demonstrated that LODDS and LNR were an independent prognostic factors, but not pN classification. The scatter plots of the relationship between LODDS and the LNR suggested that the LODDS stage had power to divide patients with the same ratio of node metastasis into different groups. For patients in each of the pN or LNR classifications, significant differences in survival could be observed among patients in different LODDS stages.ConclusionLODDS and LNR are more powerful predictors of survival than the lymph node status in patients undergoing pancreatic resection for ductal adenocarcinoma. LODDS allows better prognostic stratification comparing LNR in node negative patients.     

Prognostic value of lymph node staging in gastric cancer

BACKGROUND/AIMS: The latest TNM classification (5th edition) changed the definition of nodal staging from the anatomical localization to the total number of metastatic lymph nodes. This study was designed to evaluate and compare the prognostic significance of nodal staging between the two widely known staging systems, the TNM classification (TNM) and Japanese Classification for Gastric Cancer (JCGC). METHODOLOGY: A total of 582 patients who underwent curative gastrectomy with extended lymphadenectomy for gastric cancer were reviewed retrospectively from hospital records. Based on the localization of metastatic nodes according to the JCGC and the total positive node number according to TNM, the patients were divided into subgroups and their prognoses compared. RESULTS: Lymph node metastasis was found in 189 of the 582 patients (32.5%). Both nodal staging systems were found to be significant prognostic factors by multivariate analysis. A prognostic analysis of the patients by subdivision with the two staging systems indicated that the nodal staging system in TNM was more homogenous than that of the JCGC. CONCLUSIONS: The nodal staging system of the TNM classification is superior to that of the Japanese Classification of Gastric Cancer, because it is simple, reproducible and homogeneous.     

Prognostic analysis of patients with pancreatic head adenocarcinoma less than 2 cm undergoing resection

AIM： To investigate the differences in clinicopathological features between patients with pancreatic cancer greater or less than 2 cm situated over the pancreatic head and the prognostic factors for survival of patients with pancreatic cancer 〈 2 cm over the pancreatic head. METHODS： From 1983 to 2006, 159 patients with histologically proven pancreatic adenocarcinoma （PAC） at the pancreatic head undergoing curative resection at the Department of Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan were reviewed, comprising 123 cases of large （L）-PAC （tumor 〉 2 cm） and 36 cases of small （S）-PAC （tumor ~〈 2 cm）. We compared the clinicopathological characteristics and prognosis of L-PAC and S-PAC patients. The clinicopathological characteristics of S-PAC were investigated to clarify the prognosis predictive factors of S-PAC. RESULTS： One hundred and fifty-nine PAC patients, aged 16-93 years （median, 59.0 years） with a tumor at the pancreatic head undergoing intentional curative resection were investigated. The S-PAC and L-PAC patients had similar demographic data, clinical features, and tumor markers （a similar positive rate of carcinoembryonic antigen and carbohydrate antigen 19-9）. There were also similar rates of lymph node metastasis, portal vein invasion, stage distribution, tumor differentiation, positive resection margin, surgical morbidity and mortality observed between the two groups. During a follow-up period ranging from 1.0 to 122.7 mo （median, 10.9 mo）, S-PAC and L-PAC patients had a similar prognosis after resection （P = 0.4805）. Among the S-PAC patients group, patients with higher albumin level （〉 3.5 g/dL） had more favorable survival than those with lower albumin levels, which was the only favorable predictive prognostic factor. Meanwhile, early-staged （stage Ⅰ, Ⅱ） S-PAC patients tended to have a more favorable outcome than late-stage （stage Ⅲ, Ⅳ） S-PAC patients, but this was not statistically significant. CONCLUSION： S-PAC patients should not be regarded as early PAC. Only higher albumin level （〉 3.5 g/dL） and early stage disease （stage Ⅰ, Ⅱ） were the favorable prognosis factors for S-PAC patients.     

Prognostic value of p27 kip1 expression in adenocarcinoma of the pancreatic head region

Background. p27^kip1 is a tumour suppressor gene, functioning as a cyclin-dependent kinase inhibitor, and an independent prognostic factor in breast, colon, and prostate adenocarcinomas. Conflicting data are reported for adenocarcinoma of the pancreas. The aim of this study was to establish the prognostic value of p27^kip1 expression in adenocarcinoma of the pancreatic head region. Patients and methods. The study included 45 patients (male/female ratio 2:1; mean age 59, range 38–82 years) with adenocarcinomas of the pancreatic head region: 24 – pancreatic head, 18 – periampullary and 3 – uncinate process. The patients underwent the Kausch-Whipple pancreatoduodenectomy (n=39), pylorus-preserving pancreatoduodenectomy (n=5), or nearly total pancreatectomy (n=1). Eight patients received adjuvant chemotherapy postoperatively. Follow-up time ranged from 3 to 60 months. Tumours were staged according to the pTNM classification (UICC 1997). Immunohistochemistry was done on paraffin-embedded blocks from tumour sections. Quantitative determination of p27^kip1 expression was based on the proportion of p27^kip1 -positive cells (< 5% = negative). Survival analysis was carried out using the Kaplan-Meier method and Cox regression model. Results. Positive p27^kip1 expression was detected in 22 tumours (49%), whereas 23 tumours (51%) were p27^kip1-negative. There were no significant correlations between p27^kip1 index and stage or lymph node involvement. Median survival time in patients with p27^kip1-positive tumours was 19 months, whereas in patients with p27^kip1-negative tumours it was 18 months (p=0.53). A significant relationship was found between p27^kip1-negative tumours and radical resection (p=0.04). Multivariate survival analysis revealed that the localization of the tumour (pancreatic head/uncinate process vs periampullary) was the only significant and independent prognosticator (p = 0.01, Cox regression model). Resection margins involvement and grade remained nearly significant prognostic factors (p=0.07 and p=0.09, respectively). Conclusion. We conclude that p27^kip1 has limited overall prognostic utility in resected carcinoma of the pancreatic head region, but its potential role as a marker of residual disease needs to be further assessed.