Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index > 20%

2018 ◽  
Vol 108 (2) ◽  
pp. 109-120 ◽  
Author(s):  
Atsuko Kasajima ◽  
Björn Konukiewitz ◽  
Naomi Oka ◽  
Hiroyoshi Suzuki ◽  
Akira Sakurada ◽  
...  

The clinicopathological features of lung neuroendocrine neoplasms (NEN) with a high proliferative index at the border area between atypical carcinoid and neuroendocrine carcinoma have not been investigated so far. The aim of this study was, therefore, to search for lung NENs which are well differentiated but show Ki67 values that overlap with those of poorly differentiated (PD)-NENs. Resected lung NENs from 244 Japanese patients were reviewed, and Ki67 indices were assessed in all tumors. The data were then correlated to clinicopathological parameters and patient outcome. Among 59 (24%) well-differentiated (WD)-NENs and 185 (76%) lung PD-NENs, 7 were defined as WD-NENs with Ki67 indices > 20%. The Ki67 indices of these tumors (mean 29%, range 24–36) were significantly lower than those of PD-NENs (mean 74%, range 34–99). All WD-NENs with Ki67 > 20% lacked abnormal p53 and loss of retinoblastoma 1 (Rb1) expression. In contrast, many PD-NENs expressed p53 (48%) and showed loss of Rb1 (86%). The 2- and 5-year disease-free survival rates in WD-NEN patients with Ki67 > 20% were lower than those of WD-NEN patients with Ki67 ≤20% (p < 0.01 for disease-free and overall survival). No statistical differences were detected between outcome of WD-NEN patients with Ki67 > 20% and those of PD-NEN. It is concluded that WD-NEN patients with Ki67 > 20% share the morphological and immunohistochemical features of WD-NEN patients with Ki67 ≤20%, but they have a worse prognosis, suggesting that this tumor group requires particular attention in future classifications and probably new therapeutic regimes.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Nießen ◽  
Simon Schimmack ◽  
Marta Sandini ◽  
Dominik Fliegner ◽  
Ulf Hinz ◽  
...  

AbstractPancreatic neuroendocrine neoplasms (pNEN) are highly variable in their postresection survival. Determination of preoperative risk factors is essential for treatment strategies. C-reactive protein (CRP) has been implicated in the pathogenesis of pNEN and shown to be associated with survival in different tumour entities. Patients undergoing surgery for pNEN were retrospectively analysed. Patients were divided into three subgroups according to preoperative CRP serum levels. Clinicopathological features, overall and disease-free survival were assessed. Uni- and multivariable survival analyses were performed. 517 surgically resected pNEN patients were analysed. CRP levels were significantly associated with relevant clinicopathological parameters and prognosis and were able to stratify subgroups with significant and clinically relevant differences in overall and disease-free survival. In univariable sensitivity analyses CRP was confirmed as a prognostic factor for overall survival in subgroups with G2 differentiation, T1/T2 and T3/T4 tumour stages, patients with node positive disease and with and without distant metastases. By multivariable analysis, preoperative CRP was confirmed as an independent predictor of postresection survival together with patient age and the established postoperative pathological predictors grading, T-stage and metastases. Preoperative serum CRP is a strong predictive biomarker for both overall and disease free survival of surgically resected pNEN. CRP is associated with prognosis independently of grading and tumour stage and may be of additional use for treatment decisions.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii317-iii317
Author(s):  
Eileen Gillan

Abstract Recurrent ependymomas have a dismal prognosis (2 year survival rates 29% OS and 23% EFS) and are relatively resistant to conventional chemotherapy. We previously reported five relapsed ependymoma patients treated with a MEMMAT based metronomic antiangiogenic combination therapy. All patients are currently alive, including four patients who were multiply relapsed with at least three recurrences. These four patients received between 44–52 weeks of therapy with minimal toxicity. Three had recurrent disease within an average of 44 months (median 42 months) after discontinuation of therapy. One patient who received the following tapering bevacizumab schedule: q3 weeks x 3, q4 weeks x 4 and q5 weeks x 5 followed by maintenance therapy with fenofibrate and celecoxib is in complete remission 12 months post treatment. This regimen was well tolerated with good quality of life in this patient population. Our results suggest that the chosen anti-angiogenic drug combination prolonged the time to progression in these multiply relapsed patients and thus may be particularly beneficial for patients with recurrent ependymoma. Tapered bevacizumab and maintenance therapy with celecoxib and fenofibrate may be modifications worth further investigation for prolonged disease free survival in relapsed ependymoma patients.


2000 ◽  
Vol 18 (5) ◽  
pp. 987-987 ◽  
Author(s):  
Howard S. Hochster ◽  
Martin M. Oken ◽  
Jane N. Winter ◽  
Leo I. Gordon ◽  
Bruce G. Raphael ◽  
...  

PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma. PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1,000 mg/m2. Fludarabine 20 mg/m2 was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required. RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II/III dose (cyclophosphamide 1,000 mg/m2), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively. CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1,000 mg/m2 day 1 and fludarabine 20 mg/m2 days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients.


2010 ◽  
Vol 134 (7) ◽  
pp. 1075-1079
Author(s):  
Yvonne Saldanha Noronha ◽  
Anwar Sultana Raza

Abstract Primary, well-differentiated neuroendocrine (carcinoid) tumors of the extrahepatic biliary ducts are an uncommon cause of biliary obstruction. As compared to cholangiocarcinomas, which are more commonly seen at this location, these tumors tend to behave less aggressively, and only one-third metastasize. Tumor size (&gt;2 cm) appears to be the best predictor of aggressive behavior. Surgery is the mainstay of treatment and complete resection offers prolonged disease-free survival. Accurate preoperative diagnosis is therefore important and can be made by examining brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography and/or endoscopic ultrasound-guided fine-needle aspiration. It is important to keep this entity in mind, especially when examining cytologic or small biopsy specimens, so that appropriate immunohistochemical stains can be used to arrive at the correct diagnosis.


1987 ◽  
Vol 73 (3) ◽  
pp. 233-235 ◽  
Author(s):  
Giuseppe Muscolino ◽  
Corrado Villani ◽  
Amedeo Vittorio Bedini ◽  
Alberto Luini ◽  
Bruno Salvadori

Analysis of a series of 137 women 20–30 years of age, operated for breast carcinoma, excluding patients pregnant, lactating or with inflammatory cancer, showed that disease-free survival rates were similar and not lower than those reported for a large series of 716 breast cancer patients of all ages, treated and followed at the same Institute. Ten-year disease-free survival rates for the two series of 137 young women and 716 patients of all ages were 43.7% and 47.1% respectively. Even when considering the subgroups of patients with and without nodal axillary involvement, the corresponding figures for the two series considered were 72.6% vs. 72.1% (N−) and 25.1% vs. 24.5% (N+). It can be concluded that young age cannot be considered as an unfavorable prognostic factor.


2016 ◽  
Vol 130 (10) ◽  
pp. 948-953 ◽  
Author(s):  
T S Santos ◽  
R Estêvão ◽  
L Antunes ◽  
V Certal ◽  
J C Silva ◽  
...  

AbstractObjective:To evaluate the clinical and histopathological factors affecting the prognosis of patients with squamous cell locoregional advanced laryngeal cancer.Methods:A retrospective chart review was conducted of 121 patients with locoregional advanced laryngeal cancer, primarily treated with surgery from 2007 to 2011. Disease-free survival and overall survival rates were analysed as oncological outcomes. Prognostic variables, namely gender, pharyngeal invasion, pathological assessment of tumour and nodal stage, adjuvant therapy, margin status, nodal extracapsular extension, tumour differentiation, lymphovascular and perineural invasion, and predominant growth pattern, were also analysed.Results:One-year and three-year disease-free survival rates were 81.3 per cent and 63.5 per cent, respectively. One-year and three-year overall survival rates were 88.3 per cent and 61.4 per cent, respectively. Multivariate analysis showed that nodal extracapsular extension (p < 0.05) and an infiltrative growth pattern (p < 0.05) were associated with disease progression. Nodal extracapsular extension (p < 0.05) was associated with higher mortality.Conclusion:Nodal extracapsular extension and an infiltrative growth pattern were the main prognostic factors in locoregional advanced laryngeal cancer. The presence of pharyngeal invasion, pathologically confirmed node-positive stage 2–3 disease, close or microscopic positive margins, and lymphovascular and perineural invasion have a negative impact on prognosis.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 123-123
Author(s):  
Sylvie Lorenzen ◽  
Nils Homann ◽  
Salah-Eddin Al-Batran ◽  
Florian Lordick ◽  
Tibor Schuster ◽  
...  

123 Background: The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after treatment with preoperative docetaxel/platin /fluoropyrimidine based chemotherapy. Methods: This analysis of a prospective database identified patients who received at least one cycle of preoperative docetaxel/platin/fluoropyrimidine-based chemotherapy for at least T3/4 and N+ disease. An association of pretreatment clinicopathologic factors and pCR was investigated. Overall survival, disease-free survival and disease-specific survival were analyzed according to the achievement of a pCR. Results: A total of 120 patients received preoperative docetaxel-based chemotherapy and underwent subsequent resection of the primary tumor. 15 pts (13%) had distant metastases (M1) at initial diagnosis. 18 patients achieved a pCR in the primary (15%). Median follow-up was 41.1months. The median DFS and OS for the whole population was 24.1 and 48.6 months, respectively. DFS was significantly prolonged in pCR compared to non-pCR patients (HR 2.65, 95% CI 1.1- to 6.2; 3-year DFS probability: 71.8%±10.7 and 37.7%±5.1, respectively, P-value log-rank test=0.018). For patients with a pCR the median DFS was not reached and for those without pCR the median DFS was 22.1 months. Patients with a pCR showed an almost 50% decreased risk of death compared to non-pCR patients (HR 0.53; 95%CI 0.23 to 1.23; P=0.131). Disease-specific survival (DSS) was significantly longer in pCR vs. non-pCR patients (HR 0.188, 95%CI 0.046-to 0.77; P= 0.021). Two clinicopathological parameters were identified as predictors of pCR: tumor localization in the EGJ (p=0.019) and intestinal tumor type according to Laurén’s classification (p=0.042). Conclusions: The analysis confirms that pCR to neoadjuvant chemotherapy is a predictor of favourable patient outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ and intestinal histology represent factors significantly associated with the achievement of pCR.


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