Prevalence and Clinical Significance of Biliary Intraepithelial Neoplasia (BilIN) in Cholangiocarcinoma

Biliary intraepithelial neoplasia (BilIN) is the most common noninvasive precursor lesion which progresses to cholangiocarcinoma (CC) and is often found synchronously adjacent to the tumor or at the surgical resection margin. The aim of this study was to elucidate the prevalence and prognostic effect of BilIN on survival after resection for CC. We retrospectively analyzed the database of patients with CC who underwent surgery performed at our institution from 2010 to 2017. There were 142 patients who underwent surgery for CC. BilIN was detected in 42 patients (29.5%). On univariate analysis, extrahepatic CC (ExtraH CC) patients with BilIN lesions significantly showed better disease-free survival ( P = 0.05). Also, although not statistically significant, ExtraH CC patients with BilIN lesions revealed better overall survival (OS) ( P = 0.09). On multivariate analysis, presence of BilIN lesion, irrespective of location, was significantly associated with better disease-free survival (HR = 2.059, 95% confidence interval (CI): 1.057–4.432, P = 0.041) and OS (HR = 1.831, 95% CI: 1.149–3.534, P = 0.044) in ExtraH CC patients. The presence of BilIN lesions was not uncommon in CC patients and was significantly associated with better disease-free survival and OS in ExtraH CC patients. However, larger studies with longer follow-up are needed to accurately determine its clinical significance.

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Adult Granulosa Cell Tumors of the Ovary: A Retrospective Study of 36 FIGO Stage I Cases with Emphasis on Prognostic Pathohistological Features

Analytical Cellular Pathology ◽

10.1155/2018/9148124 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11

Author(s):

Emina Babarović ◽

Ivan Franin ◽

Marko Klarić ◽

Ani Mihaljević Ferrari ◽

Ružica Karnjuš-Begonja ◽

...

Keyword(s):

Retrospective Study ◽

Univariate Analysis ◽

Survival Rates ◽

Disease Free Survival ◽

Figo Stage ◽

Free Survival ◽

Granulosa Cell Tumors ◽

Diffuse Growth ◽

Disease Free

Objective. Adult granulosa cell tumors (AGCTs) represent 2%–5% of all ovarian malignancies. The aim of this study was to analyze clinical and pathohistological parameters and their impact on recurrence, overall, and disease-free survival in FIGO stage I AGCT patients. Methods. The tumor specimens analyzed in this retrospective study were obtained from a total of 36 patients with diagnosis of ovarian AGCT surgically treated at the Department of Gynecology, Rijeka University Hospital Centre, between 1994 and 2012. Clinical, pathological, and follow-up data were collected. Results. The mean age at diagnosis was 54.5 years with a range of 24–84. The majority of the patients, 30 (83%), were in FIGO stage IA, 3 (8%) in stage IC1, 1 (3%) in stage IC2, and 2 (6%) in stage IC3. During follow-up period (median 117.5 months, range 26–276), recurrence occurred in 4 patients (12%) with 2 deaths of the disease recorded. In univariate analysis, the 5-year survival rates were significantly shorter in patients with FIGO substage IC (p=0.019), with positive LVSI (p=0.022), with presence of necrosis (p=0.040), and with hemorrhage (p=0.017). In univariate analysis, the 5-year disease-free survival rates were significantly shorter in patients treated with fertility surgery (p=0.004), with diffuse growth pattern (p=0.012), with moderate and severe nuclear atypia (p=0.032), and with presence of hemorrhage (p=0.022). FIGO substage IC proved to be independent predictor for recurrence (OR = 16.87, p=0.015, and OR = 23.49, p=0.023, resp.) and disease-free survival (p=0.0002; HR 20.84, p=0.02) at the uni- and multivariate analyses. Conclusions. FIGO substage IC is predictive of recurrence and disease-free survival in patients with early-stage AGCTs. LVSI, presence of necrosis and hemorrhage, diffuse growth pattern, and nuclear atypia in AGCTs seem to be associated with overall and disease-free survival, so these pathological features should be taken into consideration when managing patients with AGCT.

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TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

Cell Death and Disease ◽

10.1038/s41419-021-03734-4 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Sha Zhou ◽

Jianhong Peng ◽

Liuniu Xiao ◽

Caixia Zhou ◽

Yujing Fang ◽

...

Keyword(s):

Colorectal Cancer ◽

Disease Free Survival ◽

Free Survival ◽

Epigenetic Regulator ◽

Crc Management ◽

Disease Free ◽

Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

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Phase I Study of Fludarabine Plus Cyclophosphamide in Patients With Previously Untreated Low-Grade Lymphoma: Results and and Long-Term Follow-Up—A Report From the Eastern Cooperative Oncology Group

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.5.987 ◽

2000 ◽

Vol 18 (5) ◽

pp. 987-987 ◽

Cited By ~ 62

Author(s):

Howard S. Hochster ◽

Martin M. Oken ◽

Jane N. Winter ◽

Leo I. Gordon ◽

Bruce G. Raphael ◽

...

Keyword(s):

Phase Ii ◽

Bone Marrow Involvement ◽

Survival Rates ◽

Eastern Cooperative Oncology Group ◽

Disease Free Survival ◽

Low Grade ◽

Survival Times ◽

Free Survival ◽

Disease Free

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.

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Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report

Blood ◽

10.1182/blood.v78.11.2814.2814 ◽

1991 ◽

Vol 78 (11) ◽

pp. 2814-2822 ◽

Cited By ~ 121

Author(s):

CA Linker ◽

LJ Levitt ◽

M O'Donnell ◽

SJ Forman ◽

CA Ries

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Disease Free Survival ◽

Remission Induction ◽

Cell Phenotype ◽

Free Survival ◽

Prognostic Features ◽

Adult Acute Lymphoblastic Leukemia ◽

Disease Free

Abstract We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.

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Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-002587 ◽

2021 ◽

pp. ijgc-2021-002587

Author(s):

Felix Boria ◽

Luis Chiva ◽

Vanna Zanagnolo ◽

Denis Querleu ◽

Nerea Martin-Calvo ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Quality Indicators ◽

Radical Hysterectomy ◽

Disease Free Survival ◽

Free Survival ◽

Operative Complications ◽

Early Cervical Cancer ◽

Disease Free

IntroductionComprehensive updated information on cervical cancer surgical treatment in Europe is scarce.ObjectiveTo evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database.MethodsThe SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified.ResultsThe mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) <2 cm was observed in 667 (57.7%) patients. The most frequent histology type was squamous carcinoma (794 (68.7%) patients), and positive lymph nodes were found in 143 (12.4%) patients. A total of 633 (54.8%) patients were operated by open abdominal surgery. Intra-operative complications occurred in 108 (9.3%) patients, and post-operative complications during the first month occurred in 249 (21.5%) patients, with bladder dysfunction as the most frequent event (119 (10.3%) patients). Clavien-Dindo grade III or higher complication occurred in 56 (4.8%) patients. A total of 510 (44.1%) patients received adjuvant therapy. After a median follow-up of 58 months (range 0–84), the 5-year disease-free survival was 88.3%, and the overall survival was 94.9%. In our population, 10 of the 11 surgical-related quality indicators currently recommended by ESGO were fully fulfilled 5 years before its implementation.ConclusionsIn this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

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Pituitary surgery as alternative to dopamine agonists treatment for microprolactinomas, a cohort study

Acta Endocrinologica ◽

10.1530/eje-21-0293 ◽

2021 ◽

Author(s):

Bertrand Baussart ◽

Chiara Villa ◽

Anne Jouinot ◽

Marie-Laure Raffin-Sanson ◽

Luc Foubert ◽

...

Keyword(s):

Dopamine Agonists ◽

Cox Regression ◽

Disease Free Survival ◽

Pituitary Surgery ◽

Cerebrospinal Fluid Leakage ◽

Neurosurgical Department ◽

Free Survival ◽

Kaplan Meier ◽

Disease Free

Objective: Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment. Design: Follow-up of a cohort of consecutive patients treated by surgery. Methods: Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients were presenting a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan-Meier representation. A cox regression model was used to predict remission. Results: Median follow-up was 18.2 months (range: 2.8 to 155). In this cohort, 14/114 (12%) patients were not cured by surgery, including 10 early surgical failures, and 4 late relapses occurring 37.4 months (33 to 41.8) after surgery. From Kaplan Meier estimates, 1-year and 5-year disease free survival were 90.9% (95% CI, 85.6%-96.4%) and 81% (95% CI,71.2%-92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P<0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty. Conclusions: In well selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.

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Radiofrequency Ablation of Hepatic Metastases from Colorectal Cancer: Are Newer Generation Probes Better?

The American Surgeon ◽

10.1177/000313480607201007 ◽

2006 ◽

Vol 72 (10) ◽

pp. 875-879 ◽

Cited By ~ 8

Author(s):

Aziz Ahmad ◽

Steven L. Chen ◽

Maihgan A. Kavanagh ◽

David P. Allegra ◽

Anton J. Bilchik

Keyword(s):

Colorectal Cancer ◽

Radiofrequency Ablation ◽

First Generation ◽

Hepatic Metastases ◽

Disease Free Survival ◽

Cancer Center ◽

Free Survival ◽

Alive With Disease ◽

Disease Free

Second-generation radiofrequency ablation (RFA) probes and their successors have more power, shorter ablation times, and an increased area of ablation compared with the first-generation probes used before 2000. We examined whether the use of the newer probes has improved the clinical outcome of RFA for hepatic metastases of colorectal cancer at our tertiary cancer center. Of 160 patients who underwent RFA between 1997 and 2003, 52 had metastases confined to the liver: 21 patients underwent 46 ablations with the first-generation probes and 31 patients underwent 58 ablations with the newer probes. The two groups had similar demographic characteristics. At a median follow-up of 26.2 months, patients treated with the newer probes had a longer median disease-free survival (16 months vs 8 months, P < 0.01) and a lower rate of margin recurrence (5.2% vs 17.4%); eight patients had no evidence of disease and one patient was alive with disease. By contrast, of the 46 patients treated with the first-generation probes, 2 patients had no evidence of disease and 1 patient was alive with disease. Newer-generation probes are associated with lower rates of margin recurrence and higher rates of disease-free survival after RFA of hepatic metastases from colorectal cancer.

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Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor–Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial

Journal of Clinical Oncology ◽

10.1200/jco.18.00440 ◽

2019 ◽

Vol 37 (2) ◽

pp. 105-114 ◽

Cited By ~ 21

Author(s):

Thomas Ruhstaller ◽

Anita Giobbie-Hurder ◽

Marco Colleoni ◽

Maj-Britt Jensen ◽

Bent Ejlertsen ◽

...

Keyword(s):

Breast Cancer ◽

Adverse Events ◽

Contralateral Breast Cancer ◽

Disease Free Survival ◽

Luminal Breast Cancer ◽

Free Survival ◽

Long Term Follow Up ◽

Disease Free

Purpose Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. Patients and Methods BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. Results Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. Conclusion Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

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Ecoendoscopia en la estadificación del cáncer de esófago y de estómago

Revista Argentina de Cirugía ◽

10.25132/raac.v113.n1.1524.ei ◽

2021 ◽

Vol 113 (1) ◽

pp. 32-42

Author(s):

Martín Galvarini Recabarren ◽

◽

Francisco Schlottmann ◽

C. Agustín Angeramo ◽

Javier Kerman Cabo ◽

...

Keyword(s):

Overall Survival ◽

Neoadjuvant Therapy ◽

Preoperative Staging ◽

Disease Free Survival ◽

Perioperative Chemotherapy ◽

Free Survival ◽

Causes Of Mortality ◽

Node Metastases ◽

Disease Free

Background: Gastric adenocarcinoma (GAC) and esophageal adenocarcinoma (EAC) are one of the leading causes of mortality from gastrointestinal cancer worldwide. Endoscopic ultrasound (EUS) has proved to be a valuable tool for preoperative staging of GAC and EAC in selected cases. Objective: The aim of this study was to evaluate the usefulness of EUS for staging of EAC and GAC and selecting patients who are candidates for neoadjuvant therapy, as compared with the previous stage before the implementation of EUS, in a surgical center in Argentina. Material and methods: Consecutive patients with EAC and GAC between 2013-2019 were included. Patients with criteria of unresectable cancer or who underwent emergency surgery were excluded. The sample was divided into four groups G1 and G2 (EAC with and without EUS, respectively) and G3 and G4 (GAC with and without EUS, respectively). The clinical and anatomopathological variables and survival were evaluated in all the groups. Results: A total of 89 patients were included, 40 with EAC (30 in G1 and 10 in G2, and 49 with GAC, 20 in G3 and 29 in G4. Of the patients undergoing EUS staging in G1, 23 (75%) received neoadjuvant therapy vs. 2 patients in G2 (20%) (P ≤ 0.005). Eight patients (40%) in G3 and 2 (7%) in G4 received perioperative chemotherapy (P ≤ 0.005). Lymph node metastases were observed in 9 (30%) of surgical specimens of EAC in G1 and in 60% in G2 (P ≤ 0.005), and in 45% in G3 and G4. After a mean follow-up of 36 months (6-72), we observed a non-significant trend toward higher overall survival and disease-free survival in patients undergoing EUS staging. Conclusion: EUS for preoperative staging pf EAC and GAC is a useful tool. Although the use of EUS use may be a challenging task in many centers in Argentina, future efforts are needed to include this test in selected cases for staging patients with these types of cancers

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Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre

Acta Endocrinologica ◽

10.1530/eje-18-0749 ◽

2019 ◽

Vol 180 (2) ◽

pp. 127-134 ◽

Cited By ~ 19

Author(s):

S Asioli ◽

A Righi ◽

M Iommi ◽

C Baldovini ◽

F Ambrosi ◽

...

Keyword(s):

Pituitary Adenomas ◽

Proliferative Activity ◽

Disease Free Survival ◽

Low Grade ◽

High Grade ◽

Tumour Type ◽

Disease Evolution ◽

Free Survival ◽

Disease Free

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas’ score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

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